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Theses & Dissertations: Cancer Research

Theses/dissertations from 2023 2023.

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

Functions and regulation of Ron receptor tyrosine kinase in human pancreatic cancer and its therapeutic applications , Yi Zou

Theses/Dissertations from 2011 2011

Coordinate detection of new targets and small molecules for cancer therapy , Kurt Fisher

The role of c-Myc in pancreatic cancer initiation and progression , Wan-Chi Lin

The role of inosine triphosphate pyrophosphatase (ITPA) in maintanence [sic] of genomic stability in human cells , Miriam-Rose Menezes

Molecular insights into major histocompatibility complex class I folding and assembly , Laura Christina Simone

The role of bcl-2 in colon cancer metastatic progression , Wang Wang

A rational peptidomimetic approach towards generation of high affinity BRCT (BRCA1) inhibitors , Ziyan Yuan

D-type cyclins and breast cancer , Quian Zhang

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Advances in biomarkers and techniques for pancreatic cancer diagnosis

1 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086 China

Hongli Zhang

2 Harbin Medical University, Harbin, 150086 China

3 Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086 China

4 Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Sichuan, 610500 China

Associated Data

Not applicable.

Pancreatic cancer is the most lethal type of malignancy and is characterized by high invasiveness without severe symptoms. It is difficult to detect PC at an early stage because of the low diagnostic accuracy of existing routine methods, such as abdominal ultrasound, CT, MRI, and endoscopic ultrasound (EUS). Therefore, it is of value to develop new diagnostic techniques for early detection with high accuracy. In this review, we aim to highlight research progress on novel biomarkers, artificial intelligence, and nanomaterial applications on the diagnostic accuracy of pancreatic cancer.

Introduction

Pancreatic cancer (PC) is the second leading cause of cancer-related deaths in the United States, and the estimated numbers of new cases and deaths are 60,430 and 48,220 in 2021, respectively. The 5-year survival rate is as low as 10%, despite the advent of new drugs in the past decade [ 1 ]. The imperceptible symptoms at an early-stage cause patients to miss their best chance for diagnosis and therapy. It is generally accepted that the combination of surgical resection with postoperative chemotherapy serves as the most effective strategy for PC treatment. Surgical resection alone may provide a cure for PC at an early stage, especially for tumors with a diameter less than 1 cm. Moreover, surgical resection achieved a 5-year survival rate of 80.4% for PC patients whose tumors were 1 cm or less. When PC patients have UICC stage 0, stage I A, and stage I B disease, the postoperative 5-year survival rates are 85.8%, 68.7%, and 59.7%, respectively [ 2 ].

Traditional diagnostic methods

At present, there remain challenges in developing imaging examination and tumor markers for early-stage PC diagnosis. The imaging diagnostic methods include abdominal ultrasound, CT, MRI, and endoscopic ultrasound (EUS) [ 3 ]. Ultrasound examination sometimes has difficulty accurately capturing small PC lesions due to the interference of gases in the gastrointestinal tract, preventing it from being a screening method for early-stage PC detection [ 4 ]. Enhanced CT is the first choice for the diagnosis of early-stage PC, with an overall sensitivity between 76 and 92%. However, if PC tumors less than 2 cm in diameter were included in the CT detection, the sensitivity dropped to 63–77% [ 5 ]. MRI can complement CT in the diagnosis of PC with sensitivity and specificity both at 89% [ 6 , 7 ]. The detection rates of EUS for PC in stage 0 and stage I were 45.5% and 81.8%, respectively, compared with 9.7% and 63% for CT and 9.7% and 39.1% for MRI [ 8 ]. As an invasive examination causing wounds, EUS still requires improvement for the accuracy of early-stage PC diagnosis. In addition, the diagnostic accuracy is affected by the subjectivity of different clinicians. Therefore, there is an urgent need to develop novel diagnostic agents and methods. Our review highlights the research progress of novel biomarkers, artificial intelligence technology, and new nanomaterials in the diagnosis of early-stage PC which can be resected more easily.

Advance of biomarkers related to pancreatic cancer

Serum molecules, including CA19-9, CA125, and CEA, are widely used tumor markers for routine PC detection. Serum marker detection is superior to the abovementioned traditional methods in terms of high reproducibility, good patient compliance, easy follow-up, and low cost. According to previous research, the median sensitivity and specificity of CA19-9 are 79% and 82%, respectively [ 9 ]. However, CA19-9 is not tumor type-specific because of its elevation in other malignancies, including colorectal cancer, cholangiocarcinoma, hepatocarcinoma, gastric cancer, and even benign diseases, such as obstructive jaundice, cirrhosis, cholangitis, and other gastrointestinal diseases [ 10 ]. Notably, a high CA19-9 level usually suggests advanced PC instead of early-stage PC, especially for tumors with a diameter less than 3 cm [ 11 , 12 ]. Of note, the combination of CA19-9, CEA, CA125, and CA242 showed high sensitivity and specificity for PC diagnosis, with up to 90.4% and 93.8%, respectively, which are significantly higher than the accuracy of a single serum marker [ 13 ].

Molecular biomarkers

Dna methylation.

It is believed that DNA methylation plays an important role in the initiation and progression of PC by rebalancing tumor suppressor genes and proto-oncogenes [ 14 – 16 ]. The detection of DNA methylation in peripheral blood is prevalent for PC diagnosis. Promoter DNA methylation of ADAMTS1 and BNC1 was significantly associated with PC in a cohort of 123 patients with PC, 20 patients with pancreatic intraepithelial neoplasia and 30 patients with pancreatitis, with sensitivities of 79% and 48% and specificities as high as 92% and 89%, respectively. Additionally, the sensitivity and specificity of the two-marker combination for PC diagnosis are 81% and 85%, respectively [ 17 ]. Moreover, the DNA methylation of ADAMTS1 and BNC1 was reported to be an ideal biomarker for PC TNM stage estimation. In regard to stage I PC patients, the percentages of ADAMTS1 and BNC1 DNA methylation were 87.5% and 62.5%, respectively; for stage IIa, the percentages were 77.8% and 55.6%, respectively; for stage IIb, the percentages were 90% and 65%, respectively; and for late-stage (III + IV), the percentages were almost 100%. When the two markers were used together, the percentages were 100%, 88.9%, 100%, and 100% in patients at stages I, IIA, IIB, and III/IV, respectively, suggesting an inspiring translational future [ 18 ].

Another study in Japan revealed that DNA methylation of CDO1 was related to the early diagnosis of PC based on pancreatic cytology specimens from 37 patients with PC and 6 patients with benign pancreatic disease (4 chronic pancreatitis and 2 autoimmune pancreatitis). The results showed that CDO1 promoter methylation was detected in 35/37 (94.6%) PC patients with methylation values (MV) higher than 5.0, while it was not detected in benign diseases (statistically significant, AUC = 0.96, 0.0001) [ 19 ]. Furthermore, a case–control study on CD1D DNA methylation was performed in 61 PC patients (stage I, II), 22 patients with chronic pancreatitis, and 19 healthy people with pancreatic juice specimens. Compared with healthy people and chronic pancreatitis patients, the AUC value of CD1D methylation in the pancreatic juice of PC patients was 0.92, with a sensitivity of 75% and a specificity of 95% [ 20 ]. The DNA methylation of biomarkers for PC detection is displayed in Table ​ Table1 1 .

DNA methylation of biomarkers for PC detection

Noncoding RNAs

Noncoding RNAs play important roles in PC development. In a study of blood samples from 409 PC patients, 25 chronic pancreatitis patients, and 312 healthy people, ectopic expression of microRNAs was found in the serum of PC compared with chronic pancreatitis and healthy people. Compared with the control, 38 microRNAs were detected with ectopic expression in early-stage PC patients, and 14 were used to set up two panels for diagnosis (Panel I: miR-145, miR-150, miR-223, miR-636; Panel II: miR-26b, miR-34a, miR-122, miR-126, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885-5p). The two panels were applied to a validation cohort including 180 cases of PC, 1 patient with chronic pancreatitis, and 199 healthy controls. The AUC of Panel I was 0.86, and the diagnostic sensitivity was 85% with a specificity of 64%. Panel II achieved an AUC of 0.93, diagnostic sensitivity of 85% and specificity of 85%. In addition, the panel combined with CA19-9 could further improve the diagnostic efficiency. The AUC of Panel I plus CA19-9 increased to 0.94 (P = 0.01), and Panel II could be up to 0.93 [ 21 ]. Except for the above panels, there were many miRNAs that were demonstrated to contribute to the diagnosis of early-stage PC, such as a panel containing 6‐miRNAs (let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p and miR‐25-3p), serum miR-25 combined with CA19-9, and miR-17-5p methylation, which was superior to CA19-9 or CEA [ 22 – 24 ]. Except for pancreatic tissue and blood, miRNA dysregulation was also detected in feces, urine, and saliva, which are easy to obtain by noninvasive methods [ 25 ]. In urine, the levels of miR-143, miR-223 and miR-30 were higher at stage I, and the combination of miR-143 and miR-30 showed high sensitivity and specificity with 83.3% and 96.2%, respectively [ 26 ]. In stool, Yang et al. reported that the levels of miR-21 and miR-155 were much higher in PC patients than in healthy controls [ 27 ]. Recently, salivary miRNAs were demonstrated to be stable due to the protection of exosomes or protein complexes, thus showing their promising roles as diagnostic markers. For example, miR-1246 and miR-4644 in saliva had ROC curves with AUC = 0.814 (P = 0.008) and 0.763 (P = 0.026), respectively, for distinguishing PC patients from healthy controls. Additionally, their combination increased the AUC to 0.833 (P = 0.005) [ 28 ]. The efficacy of microRNAs in the differential diagnosis of PC from healthy participants is displayed in Table ​ Table2 2 .

Efficacy of microRNAs in the differential diagnosis of pancreatic cancer from healthy participants

C* = CA19-9. Panel I is composed of miR-145, miR-150, miR-223, miR-636; Panel II is composed of miR-26b, miR-34a, miR-122, miR-126, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885-5p; six‐miRNA panel contains let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐253p

In addition to microRNAs, long noncoding RNAs may also serve as effective biomarkers for early-stage PC detection. For example, compared with healthy controls, the SNHG15 level is higher in PC patients and contributes to cell proliferation via H3K27me3 mediated by EZH2 [ 29 ]. In addition, SNHG15 expression in serum exerts a moderate diagnostic value with a sensitivity of 68.3% and a specificity of 89.6% [ 30 ]. Plasma lncRNA Linc-pint was significantly decreased in PC patients compared with healthy volunteers, as well as in carcinoma of the ampulla of Vater and cholangiocarcinoma. Therefore, Linc-pint might be used for identifying the cause of malignant obstructive jaundice and helping to trace the cancer origin [ 31 ].

Circular RNAs (circRNAs) have continuous closed circular structures, making them stable enough to serve as molecules for cancer detection [ 32 ]. Circ-LDLRAD3 was significantly increased in PC tissues and plasma, and markedly related to lymphatic invasion, venous invasion, and metastasis. Although circ-LDLRAD3 is not an ideal independent biomarker, its combination with CA19-9 showed an increase in AUC from 0.87 to 0.67, and the sensitivity and specificity were 80.33% and 93.55%, respectively [ 33 ]. The circRNAs IARS and PDE8A that are contained in the plasma exosome were upregulated and associated with the progression and prognosis of PC, and are likely to be promising biomarkers in the detection of early-stage PC [ 34 , 35 ]. In addition, compared with the healthy controls, circ-001569 levels were higher in 26 tumor tissues and 97 plasma samples of PC patients (P < 0.01) [ 36 ]. Table ​ Table3 3 shows the efficacy of lncRNAs or circRNAs in the differential diagnosis of PC from healthy participants.

Efficacy of lncRNAs or circRNAs in the differential diagnosis of pancreatic cancer from healthy participants

Proteomic biomarkers

Proteomics is based on the study of the full set of proteins and aims to understand all expressed proteins in cells, including their number, level, and renewal. Protein biomarkers related to PC can be detected in the patient’s blood, pancreatic juice, and tumor tissue [ 37 ].

Aberrant levels of GPC1, CPA4, C4BPA, PFAA, MUC5AC, and OPNT + TIMP-1 were frequently detected in the serum of PC patients. Melo’s team found that the level of GPC1 in exosomes from the blood of PC patients was significantly higher than that in exosomes from patients with benign pancreatic diseases and healthy people. In addition, the GPC1 expression level is positively correlated with the tumor burden [ 38 ]. Similarly, Sun et al. affirmed the potential of CPA4 as a great biomarker of PC. They compared the serum levels between PC patients (n = 100) and healthy patients (n = 50). The results suggested that PC patients had significantly greater serum levels of CPA4 than patients in the healthy group (1.695 ± 2.093 vs. 0.123 ± 0.251 ng/mL, P = 0.000) [ 39 ]. Notably, C4BPA is superior to CA19-9 in sensitivity and specificity in the early diagnosis of PC [ 40 ]. PFAA also has a strong correlation with the stage of PC and could be used as a pathological diagnostic reference [ 41 ]. Sukhwinder et al. supported MUC5AC as a valuable biomarker for PC detection. MUC5AC exhibited satisfactory sensitivity and specificity when used in the differential diagnosis among PC, benign pancreatic disease, and chronic pancreatitis. A similar function was also shown when MUC5AC was combined with CA19-9 [ 42 ]. Serum osteopontin and tissue inhibitor of metalloproteinase 1 (OPNT + TIMP-1) combined with CA19-9 in blood also displayed potential to improve the sensitivity of PC diagnosis [ 43 ]. In regard to the protein markers in urine samples, the levels of LYVE1, REGIA, and TFFI were significantly related to PC. The accuracy exceeds 90% for the early diagnosis of PC; thus, it showed an ideal clinical impact, although it still requires a large cohort for validation [ 44 ]. In addition, neutrophil gelatinase-associated lipocalin (NGAL) in urine provides a clue for the early diagnosis of PC [ 45 ].

In pancreatic juice, the upregulation of anterior gradient-2 (ARG2) implied its role as a marker for PC diagnosis [ 46 ]. However, the acquisition of pancreatic juice requires an invasive method, which is not widely accepted. Moreover, the bile component could be used to detect early-stage PC with high sensitivity [ 47 ]. It was reported that LDL receptor-related with 11 ligand-binding repeats (sLR11) in the bile of PC patients has the potential to distinguish PC from healthy controls [ 48 ]. All of the above biomarkers from different clinics for PC diagnosis are summarized in Fig.  1 .

Biomarker candidates for the diagnosis of pancreatic cancer from easy-to-obtain samples in clinics, including saliva, pancreatic juice and bile, serum, feces, and urine. *Panel I = miR-145, miR-150, miR-223, miR-636 **Panel II = miR-26b, miR-34a, miR-122, miR-126, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885-5p

Artificial intelligence (AI)

The diagnosis of PC by traditional imaging methods and pathological slices requires experts to perform complex analyses on a large amount of data. Due to differences in physician training, experience, and professional qualities, the results of diagnosis are partly influenced by the subjectivity of doctors. Therefore, it is crucial to develop an automatic and accurate imaging processing technology that requires less manual intervention [ 49 ]. In recent years, AI techniques have revolutionized the medical field. With the help of AI technology, tedious image analysis, subjective differences of doctors, and inconsistent diagnosis can be avoided [ 50 ]. AI technology is capable of accelerating image processing while maintaining consistency and high accuracy.

The conceptual category of AI primarily includes machine learning (ML) and deep learning (DL) [ 51 ]. ML is a multifield interdisciplinary subject involving subjects such as probability theory and statistics. ML specializes in the study of how computers simulate or implement human learning behaviors to acquire new knowledge or skills and reorganize the existing knowledge structure to continuously improve its performance. DL learns the internal laws and representation levels of sample data. These learning processes are very helpful for the interpretation of many texts, images, and sounds. DL is also composed of a variety of deep neural networks, with tremendous reports on its application in the recognition of lung cancer, prostate cancer, and rectal lymph node images with satisfactory results [ 52 – 54 ]. Another successful model is the deep convolution neural network (DCNN), which has been shown to improve the diagnostic precision of thyroid cancer by analyzing clinical ultrasound sonographic imaging results. Compared to a group of professional radiologists, the model showed comparable sensitivity and increased specificity concerning the detection of patients with thyroid cancer [ 55 ]. At present, AI has been applied in the field of imaging intelligent diagnosis of pancreatic diseases with significant progress [ 56 , 57 ].

AI utilization in PC diagnosis

Ai utilization in imaging.

For CT and MRI, AI has been used to facilitate diagnostic accuracy [ 58 , 59 ]. The computer learning based on a convolutional neural network (CNN) from 370 PC patients and 320 non-PC patients showed a more superior diagnostic efficiency than radiologists, with an accuracy of 0.986–0.989. The sensitivity of CNN was also higher than that of radiologists (0.983 vs. 0.929; p = 0.014). However, during the test, the CNN technique missed 3 tumors with a diameter < 15 mm, 2 of which were discovered by radiologists. The radiologist missed 12 tumors with a diameter ranging from 10 to 33 mm, while the CNN accurately diagnosed 11 of them. Liu et al. used the CNN method to interpret contrast-enhanced CT images of 338 PC patients (238 as the training set with 4385 images and 200 patients with 1699 images as the validation group) [ 60 ]. The R-CNN model was used to classify the recognized images. The true-positive rate (TPR), false-positive rate (FPR), precision (P), and recall rate (R) were obtained according to whether the sample was accurately identified and the coverage rate of the identification. Subsequently, the average value of average precision (AP) for each group was obtained. The mean AP of the R-CNN for 4385 image recognition for training was 0.7664. The receiver operating characteristic (ROC) curve for the validation group showed the area under the curve (AUC) according to the trapezoidal rule to be 0.9632. These results highlight the effectiveness of AI in the auxiliary diagnosis of PC. The team also noticed that AI only took 0.2 s to recognize one CT image and 3 s to finish the image recognition of one patient, which is much faster than the average recognition time of a well-trained imaging doctor (average 8 min) [ 61 ]. Furthermore, Gao et al. also used the CNN model to identify MRI images with a 0.90 AUC of PC [ 62 ]. The combination of PET/CT images with AI technology used the support vector machine-random forest (SVM-RF) + dual-threshold principal component analysis (DT-PCA) model to detect PC. The sensitivity/specificity/accuracy was as high as 95.2%/97.5%/96.5%, suggesting that the diagnostic efficiency of PET-CT was significantly improved with the assistance of AI [ 63 ].

The major difficulty for EUS-AI applications is that different lesions often have similar imaging findings. The subjectivity of the surgeon is also a factor, causing a certain proportion of misdiagnoses and missed diagnoses. Based on the principle of pixels, AI can reduce subjectivity by integrating the changes in the lesion structure with digital image analysis. In a controlled experiment from Das et al., they established an artificial neural network (ANN) based on different pathological types of PC, chronic pancreatitis, and normal pancreas. The ANN model displayed a high sensitivity/specificity/AUC of 93.0%/92.0%/93% for PC detection, as well as a perfect discrimination of normal pancreas and chronic pancreatitis (sensitivity, specificity, and accuracy are as high as 100%) [ 64 ]. Zhu et al. conducted a comparative analysis of 262 cases of PC and 126 cases of chronic pancreatitis, including the support vector machine model’s recognition of 16 EUS images for each patient. The sensitivity/specificity/accuracy of the model is up to 91.6%/95.0%/94.2% for PC detection [ 65 ]. The ANN model for the enhanced EUS images in another study showed that vascular parameters can distinguish PC and chronic pancreatitis cases with a sensitivity of 94.64% and a specificity of 94.44% [ 66 ].

AI utilization in pathology

AI attempts to use computer models for pancreatic cytological diagnosis, especially on samples from endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). The images of cell cluster fragments under pathological slices were obtained under the analysis from a mobile neural network (MNN) model to distinguish benign and malignant cells with features [ 67 ]. These features are surprisingly similar to those recognized by cytopathologists. This suggests that MNN have comparable accuracy with pathologists in their preliminary judgments on cell images. The study also showed an MNN model of 80% for the sensitivity of the FNA results that the pathologist could not determine. Collectively, these findings indicate the MNN model is a promising tool for pancreatic FNA specimen screening and reducing the limitations of pathologists’ subjective judgment.

AI utilization in biomarkers

AI can also be applied for the analysis of biological markers [ 68 ]. In a study with AI to analyze serum tumor markers (CA19-9, CA125, CEA), the 913 serum samples from PC patients and non-PC patients were randomly divided into a training group (sample size of 658) and a test group (sample size of 255). They established an ANN model for PC diagnosis in the training group and validated the model in the test group. The results showed that the AUC of PC was as high as 0.91. Compared with the AUC (CA19-9: 0.845, CA125: 0.795, CEA: 0.800) of a single tumor marker obtained under the Logistic Regression model, the ANN model displayed a better diagnostic performance [ 69 ]. Researchers used a smoothly clipped absolute deviation-based penalized support vector machine to build a PC diagnosis model in another study, with 39 miRNA markers in blood serum samples from 63 PC patients and 63 control subjects as the training cohort, and it was validated in an additional group with 25 PC samples and 81 intrahepatic cholangiocarcinoma samples. The AUC, sensitivity (96.0%), and specificity (90.0%) of the proposed diagnostic model were 1.5, 1.3, and 2 times higher than those of the CA19-9 diagnosis model, respectively [ 70 ]. Although the individual miRNAs were not specific to PC, the combination of all 39 miRNA markers enabled a high diagnostic specificity. The diagnostic power of the individual models is summarized in Table ​ Table4 4 .

Applications of AI in the diagnosis of pancreatic cancer

Application of nanomaterials in the diagnosis of pancreatic cancer

Novel nanomaterial components are believed to act as a powerful tool for improving the sensitivity and specificity of early-stage cancer detection [ 71 – 74 ].

Nanomaterials as contrast agents

The addition of novel designed nanoparticles (NPs) to contrast agents could overcome the limitations of first-generation organic contrast agents by increasing sensitivity through better biodistribution [ 75 ]. In 2015, Rosenberger et al. modified the nanoparticle of a peptide with a high affinity to galectin-1, which is highly expressed in PC cells, thus making it an ideal MRI contrast agent [ 76 ]. Luo et al. also reported a new type of nanocontrast agent—iron oxide NPs (IONPs), which were encapsulated in HA-Fe 3 O 4 -NPs (hyaluronic acid-mediated multifunctional Fe 3 O 4 nanoparticles) with fluorescein isothiocyanate (FITC) together to capture the NP by using the principle of selective recognition of hyaluronan by CD44 receptor [ 77 ]. In both cases, the accumulation of NP in the tumor increased the detection accuracy by MRI. In terms of safety, IONPs are superior to the current organic contrast agents used in toxic reduction [ 78 ].

Another nanomaterial contrast agent named AuNR–SiO 2 –GD NPs was injected into PC-bearing albino mice followed by CT and MRI examinations, showing an increased contrast effect, higher detection sensitivity, more accurate target biodistribution, and more accurate spatial and temporal resolution. In terms of safety, the contrast agent accumulated in the liver without damage [ 79 – 81 ].

Nanomaterials as sensitizers of biomarkers

Another team tried carbon nanotubes (CNTs) carrying CA19-9 antibody and performed detection experiments on CA19-9 at different concentrations. The results showed that the CNT-based detection threshold was 100 times lower than that of the traditional ELISA method. Therefore, it is possible that CNTs may detect changes in CA19-9 levels at the early stage of PC [ 82 ]. Multiwalled carbon nanotubes (MWCNTs) developed by another lab were used as a sensitive biosensor carrier to detect low levels of CA19-9 [ 83 ]. The specific antibody attached to the surface of MWCNTs on the test paper was able to detect CA19-9 at a concentration of 0–1000 U/mL in the blood sample.

Quantum dots (QDs) are also a type of nanoparticle used to detect cancer. The fluorescence excitation wavelengths of QDs range from 400 to 2000 nm, and the size and composition of QDs can be adjusted for application. This characteristic makes it possible for a single light source to detect and track multiple biomarkers at the same time [ 84 ]. Furthermore, QDs are reusable and have a longer line span due to their fading resistance [ 85 ]. ZnO QDs, as electrochemical and fluorescent labels, are used for the detection of the PC biomarker CA19-9 by an immunosandwich method with high sensitivity, selectivity, and stability. Based on the bioconjugation of ZnO QDs and the CA19-9 antigen-antibody immunoreaction, sandwich immunosensors were assembled on a functional Si substrate for CA19-9 detection. Immune recognition of CA19-9 was converted into amplified signals of square wave stripping voltammetry and intrinsic photoluminescence. In this way, the peak intensity of square wave voltammetry rose with an increase in CA 19-9 concentrations, showing a broad linear response range from 0.1 to 180 U/mL in logarithmic styles [ 86 ]. The detection limit of 0.1 U/mL CA 19-9 is far less than the threshold concentration in clinical diagnosis value of 35 U/mL, suggesting the power in the diagnosis of PC at an early stage.

Nanomaterials as diagnostic probes for PC

The monodispersed organically modified space silica (ORMOSIL) nanoparticles, which were covalently conjugated with the fluorophore rhodamine, presented a variety of active groups on their surface and were used to detect early-stage PC. The carboxyl groups on the surface were conjugated to bioactive molecules, such as monoclonal antibodies, to target unique antigen molecules on PC cells. ORMOSIL nanoparticles entered PC cells in a receptor-mediated manner. Detection of the conjugated fluorophore rhodamine showed that the uptake of nanoparticles conjugated with anti-claudin 4, anti-mesothelin, and transferrin was much higher in PC cells than in control cells (more than 90% vs. 55.9%). In addition, ORMOSIL selectively targeted tumor cells and did not show any cytotoxicity in vitro [ 87 ]. Therefore, the property of the fluorescent ORMOSIL nanoparticles showed potential applications for optical bioimaging as effective probes for diagnosis in vivo. The functions of various nanomaterials are summarized in Table ​ Table5Table 5 .

The function of nanomaterials for PC detection

Future perspective

There is a debate about finding a sensitive biomarker to replace CA19-9 for predicting early-stage PC. Emerging novel biomarkers and AI techniques in imaging have enabled the precision diagnosis of early-stage PC in recent decades. As genetic changes are prevalent in the initiation and progression of PC, molecular biomarkers, including DNA methylation, noncoding RNAs, and proteins from peripheral blood or pancreatic juice, exerted their roles as indicators in PC detection. However, there remains many limitations for clinical translation due to the inconsistence of sensitivity and specificity. DNA methylation seems to have a very stable detection rate, but methylation did not have a very strong relationship with early-stage PC. The dysregulation of noncoding RNAs was intensively investigated and detected in blood, feces, urine, or saliva, which were more acceptable by the patients, compared with other invasive detection methods, such as EUS and FNA. Moreover, circRNAs showed great stability in body fluids, making them ideal biomarkers for PC diagnosis. To further enhance the sensitivity and specificity of early detection, an effective cocktail combination model should be developed before clinical translational validation.

AI is mainly used for the recognition of images of CT, MRI, EUS, and pathology examinations. The identification accuracy of AI depends on not only the construction and optimization of the neural network model but also the size of the dataset used for training. AI already helps pathologists overcome tedious image analysis, eliminate subjective differences, and enhance diagnosis consistency. In many cases, AI performance is superior to pathologists in cytomorphology. In this aspect, AI can be used to judge pancreatic FNA specimens or cells in pancreatic juice that pathologists cannot determine and provide a reference value for the early diagnosis of the disease, improving early intervention for PC.

Nanomaterials have attracted much attention in the field of medical diagnosis as contrast agents for imaging examination with a high affinity for PC cells due to their conjugated active molecules on the surface. In addition, nanomaterials have better biodistribution, contrast enhancement, and safety in the human body than traditional contrast agents. Nanomaterials can also be modified with antibodies, which can bind specifically to biomarkers on cells. The PC serum biomarker detection system combined with nanomaterials has a much wider range of detection and a lower detection threshold, which is probably significant in the diagnosis of early-stage PC. Nanoparticles conjugated with fluorescence could help in the optical bioimaging of PC, but the intensity remains a problem. Importantly, most nanomaterials are in the laboratory research stage and have not been tested in trials. There is still a long way before clinical application of nanomaterials because of their potential toxicity, side effects, and efficacy in humans.

At present, these new diagnostic methods also have great potential to be put into clinical practice. The new biomarkers detecting PC depend on the technology of fluid biopsy, which can perform a non-invasive examination in peripheral blood or exocrine fluids. The critical step in putting these new biomarkers into clinical practice is developing efficient and sensitive test kits. In the past, the gold standard for testing DNA methylation was bisulfite sequencing. However, this method also had the defects of low accuracy and poor repeatability, while a kind of digital PCR (dPCR) technology currently under research could overcome the above limitations, and the kits based on this technology have good clinical prospects. Meanwhile, simple and sensitive single-molecule fluorescence technology has made great progress in detecting noncoding RNAs. However, it is limited to detecting the nucleic acids from extracellular fluid, but some relevant nanosensors can detect noncoding RNAs in the living cells. It is possible to attain the clinical practice of testing noncoding RNAs by the above two modes. Moreover, the routine immunohistochemical technology could be used in the detection of novel proteomic biomarkers according to the combination of antigens and antibodies in peripheral blood, saliva, urine, feces and pancreatic juice. Increasing the volume of collected specimens, and developing concentration technology may be a solution to developing applicable clinical apparatus based on the multiple characteristics of new biomarkers. In addition, the digital pathology with AI technology has made great progress, which can realize a series of functions such as image collecting, image preprocessing, image segmentation, feature acquisition, image classification and recognition. The pathological and cytological robots based on the above techniques have been well applied to the cytological examination and the rapid freezing pathological detection to improve the accuracy and speed of diagnosis. Significantly, the application of AI technology does not mean that it can completely replace the roles of medical practitioners in the judgment of diseases, which is only used as a reference in clinical practice. At the same time, an AI corrective system for diagnosis should also be established to check the conclusion of clinicians in time and improve the accuracy of diagnosis. Furthermore, when the nanomaterials are used as contrast agents in the imaging examination of PC, it is feasible to improve the safety by means of controlling the size of nanomaterials before clinical practice. Using biocompatible molecules such as folic acid or glucose to modify the nanomaterials may also improve the compatibility of human tissue or increase the binding affinity to cancer cells. The diagnostic probes which are rich in nanomaterials can play their optical characteristics to locate the PC lesions or conduct immunofluorescence labeling for final clinical practice.

The question of how to diagnose PC earlier is always a motivation for researchers. Screens for early-stage PC need more sensitive and tumor-type specific biomarkers. The ideal method of biomarker detection should be less affected for patients and simple to conduct by clinicians. With the advancement of algorithms and neural network models, AI-assisted PC diagnosis will be used widely in clinical practice. The ultimate goal of AI techniques is to allow machines to have the ability to analyze and learn like humans and make diagnostic decisions for clinicians. The improvement of current methods and the development of novel concepts for diagnosis are necessary for the near future (Fig.  2 ).

Potential clinical applications for the diagnosis of A pancreatic cancer, including B new biomarkers, C Artificial intelligence (AI), and D nanomaterias. As shown in Part B , samples were obtained from urine, blood, saliva, and feces such as B-1 ; new biomarkers included DNA methylation such as B-2 , proteomic biomarkers such as B-3 , and noncoding RNAs such as B-4 . AI is shown in Part C . AI utilization can be used in imaging such as C-2 , pathology such as C-3 and recognition of biomarkers such as C-4 for PC detection. Part of D describes the application of nanomaterials for the diagnosis of PC; they can play a role as contrast agents such as D-2 , diagnostic probes such as D-3 , and sensitizers of biomarkers such as D-4

With the progress of research, we believe that imaging examinations, biomarker tests and other novel methods for early-stage PC diagnosis would benefit the PC patient survival rate.

Acknowledgements

Abbreviations, author contributions.

HW and SO, manuscript draft and figure preparation. HZ, literature research. RH, proof reading and figure preparation. SY, MZ and ST, concept design, funding acquisition, manuscript revision. All authors read and approved the final manuscript.

1. National Natural Science Foundation of China: 81872034, 81972724. 2. Natural Science Foundation of Heilongjiang Province: H2017016. 3. Wu Jieping Medical Foundation: 320.6750.19092-41. 4. Chen Xiao-ping Foundation for The Development of Science and Technology of Hubei Province: CXPJJH12000002-2020025. 5. Training Program of Innovation and Entrepreneurship for Undergraduates in Heilongjiang Province: S202010226061.

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Haotian Wu and Suwen Ou contributed equally to the article

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Improving outcomes in patients with a diagnosis of pancreatic cancer

• Rille Pihlak
• Division of Cancer Sciences

Student thesis : Phd

• pancreatic cancer
• cancer outcomes
• hyperglycaemia
• patients views on outcomes

File : application/pdf, -1 bytes

Type : Thesis

• Search for: Search
• Seema Chugh, PhD

Scientist II, Hale Family Center For Pancreatic Cancer Re search

Bio       Research Interests       Key Publications

Dr. Seema Chugh obtained her Bachelor of Science degree in Biochemistry from Panjab University, India, followed by a master’s program in Biochemistry at All India Institute of Medical Sciences (AIIMS, India). She completed her PhD in Biochemistry and Molecular Biology at the University of Nebraska Medical Center (Omaha, USA), where she relocated to the United States in 2012 to pursue her passion for cancer research. During her doctoral studies, she focused on Pancreatic Cancer glycobiology, leading to the development of the first genetically engineered mouse model of pancreatic cancer with aberrant O-glycosylation (KPCC mice). Her research work was published in Gastroenterology and featured on the cover of the November 2018 issue.

To further advance her research interests in basic and translational cancer research, Dr. Chugh joined the esteemed research lab of Dr. Arul Chinnaiyan (Rogel Cancer Center, University of Michigan, USA) as a Post-Doctoral fellow in Jan 2018. Her research work in Chinnaiyan lab was centered on KRAS-driven cancers, an area that until recently lacked small molecule inhibitors targeting KRAS directly. In the Chinnaiyan lab, she led multiple projects that were focused on RAS biology and cancer therapeutics.  Her team conducted an exhaustive analysis of proteins interacting with KRAS, revealing Argonaute 2 (AGO2) as a binding partner. To delve deeper into the functional implications of this interaction, she characterized mouse models of pancreatic and lung cancer with knockout of Argonaute 2 (AGO2). Remarkably, in her studies with the pancreatic cancer model, the deletion of AGO2 halted the progression from Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC). In parallel to KRAS biology, she also explored therapeutics and analyzed the efficacy of a Phase Ia-cleared, orally bioavailable dual ALK and focal adhesion kinase (FAK) inhibitor, ESK440, in multiple preclinical models of cancer. In addition to her research endeavors, Dr. Chugh has mentored several undergraduate students and helped them in achieving their career goals.

After gaining extensive experience in pancreatic cancer research, KRAS biology, and genetically engineered mouse models, Dr. Chugh joined as Scientist II in Andrew Aguirre’s lab and Hale Family Center for Pancreatic Cancer Research, Dana Farber Cancer Institute (DFCI).

Research Interests

Dr. Seema Chugh has been researching KRAS-driven cancers for over a decade (2012-Current). KRAS is mutated in more than 90% of PDAC patients and is the predominant driver of pancreatic cancer. Dr. Chugh spearheads the RAS therapeutic efforts in the pancreatic cancer center and Aguirre lab. She and her team are working on diverse RAS inhibitors (KrasG12D, pan-KRAS, and multi-RAS), procured from several biotech firms. Some of these compounds are currently undergoing early clinical trials.

Dr. Chugh is deeply committed to advancing pancreatic cancer therapeutics by accelerating preclinical research on KRAS inhibitors. Her focus extends to thoroughly exploring their therapeutic potential, understanding their mechanisms of action, and identifying resistance mechanisms to inform potential combination therapies. Concurrently, she supervises several research technicians, postdoctoral fellows, and clinical fellows in the Aguirre lab. Additionally, she leads the Hale Center Model core, which encompasses a biobank of patient-derived organoid models and various mouse models of pancreatic cancer.

Key Publications

Siebenaler RF*, Chugh S * , Waninger JJ, Dommeti VL, Kenum C, Mody M, Gautam A, Patel N, Chu A, Bawa P, Hon J, Smith RD, Carlson H, Cao X, Tesmer JJG, Shankar S, Chinnaiyan AM. Argonaute 2 modulates EGFR-RAS signaling to promote mutant HRAS and NRAS-driven malignancies. PNAS Nexus . 2022 Jul 28;1(3): pgac084. (*Co-first Authors)

Tien JC*, Chugh S *, Goodrum A, Cheng Y, Mannan R, Zhang Y, Wang L, Dommeti VL, Wang X, Xu A, Hon J, Kenum C, Su F, Wang R, Cao X, Shankar S, Chinnaiyan AM. AGO2 promotes tumor progression in KRAS-driven mouse models of non-small cell lung cancer. Proc Natl Acad Sci U S A. 2021 May 18;118(20): e2026104118. ( *Co-first Authors )

Shankar S*, Tien JC*, Siebenaler RF*, Chugh S *, Dommeti VL, Zelenka-Wang S, Wang XM, Apel IJ, Waninger J, Eyunni S, Xu A, Mody M, Goodrum A, Zhang Y, Tesmer JJ, Mannan R, Cao X, Vats P, Pitchiaya S, Ellison SJ, Shi J, Kumar-Sinha C, Crawford HC, Chinnaiyan AM. An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development. Nature Communications . 2020 Jun 4;11(1):2817. (*Co-first Authors)

Gupta R, Leon F, Thompson CM, Nimmakayala R, Karmakar S, Nallasamy P, Chugh S , Prajapati DR, Rachagani S, Kumar S, Ponnusamy MP. Global analysis of human glycosyltransferases reveals novel targets for pancreatic cancer pathogenesis. Br J Cancer . 2020 May;122(11):1726.

Barkeer S, Chugh S , Karmakar S, Kaushik G, Rauth S, Rachagani S, Batra SK, Ponnusamy MP. Novel role of O-glycosyltransferases GALNT3 and B3GNT3 in the self-renewal of pancreatic cancer stem cells. BMC Cancer . 2018 Nov;18(1):1157.

Chugh S , Barkeer S, Rachagani S, Nimmakayala RK, Perumal N, Pothuraju R, Atri P, Mahapatra S, Thapa I, Talmon GA, Smith LM, Yu X, Neelamegham S, Fu J, Xia L, Ponnusamy MP, Batra SK. Disruption of C1galt1 Gene Promotes Development and Metastasis of Pancreatic Adenocarcinomas in Mice. Gastroenterology . 2018 Nov;155(5):1608-1624; Featured on the Issue Cover

Barkeer S, Chugh S , Batra SK, Ponnusamy MP. Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis. Neoplasia . 2018 Aug;20(8):813-825.

Nimmakayala RK, Seshacharyulu P, Lakshmanan I, Rachagani S, Chugh S , Karmakar S, Rauth S, Vengoji R, Atri P, Talmon GA, Lele SM, Smith LM, Thapa I, Bastola D, Ouellette MM, Batra SK, Ponnusamy MP. Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1. Gastroenterology . 2018 Sep;155(3):892-908.e6.

Muniyan S, Haridas D, Chugh S , Rachagani S, Lakshmanan I, Gupta S, Seshacharyulu P, Smith LM, Ponnusamy MP, Batra SK. MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. Genes Cancer . 2016 Mar;7(3-4):110-124.

Chugh S , Meza J, Sheinin YM, Ponnusamy MP, Batra SK. Loss of N acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer: augmented aggressiveness and aberrant ErbB family glycosylation. Br J Cancer . 2016, Jun 14;114(12):1376-86.

Chugh S , Gnanapragassam VS, Jain M, Rachagani S, Ponnusamy MP, Batra SK. Pathobiological implications of mucin glycans in cancer: Sweet poison and novel targets. Biochim Biophys Acta . 2015 Dec;1856(2):211-25.

Rachagani S, Macha MA, Heimann N, Seshacharyulu P, Haridas D, Chugh S , Batra SK. Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer. Adv Drug Deliv Rev. 2015 Jan; 81:16-33.

Haridas D, Ponnusamy MP, Chugh S , Lakshmanan I, Seshacharyulu P, Batra SK. MUC16: molecular analysis and its functional implications in benign and malignant conditions. FASEB J. 2014 Oct;28(10):4183-99.

Ponnusamy MP, Seshacharyulu P, Lakshmanan I, Vaz AP, Chugh S , Batra SK. Emerging role of mucins in epithelial to mesenchymal transition. Curr Cancer Drug Targets. 2013 Nov;13(9):945-56.

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• 12 March 2024

Bring PhD assessment into the twenty-first century

You have full access to this article via your institution.

Innovation in PhD education has not reached how doctoral degrees are assessed. Credit: Dan Dunkley/Science Photo Library

Research and teaching in today’s universities are unrecognizable compared with what they were in the early nineteenth century, when Germany and later France gave the world the modern research doctorate. And yet significant aspects of the process of acquiring and assessing a doctorate have remained remarkably constant. A minimum of three years of independent study mentored by a single individual culminates in the production of the doctoral thesis — often a magisterial, book-length piece of work that is assessed in an oral examination by a few senior academic researchers. In an age in which there is much research-informed innovation in teaching and learning, the assessment of the doctoral thesis represents a curious throwback that is seemingly impervious to meaningful reform.

But reform is needed. Some doctoral candidates perceive the current assessment system to lack transparency, and examiners report concerns of falling standards ( G. Houston A Study of the PhD Examination: Process, Attributes and Outcomes . PhD thesis, Oxford Univ.; 2018 ). Making the qualification more structured would help — and, equally importantly, would bring the assessment of PhD education in line with education across the board. PhD candidates with experience of modern assessment methods will become better researchers, wherever they work. Indeed, most will not be working in universities: the majority of PhD holders find employment outside academia.

Collection: Career resources for PhD students

It’s not that PhD training is completely stuck in the nineteenth century. Today’s doctoral candidates can choose from a range of pathways. Professional doctorates, often used in engineering, are jointly supervised by an employer and an academic, and are aimed at solving industry-based problems. Another innovation is PhD by publication, in which, instead of a final thesis on one or more research questions, the criterion for an award is a minimum number of papers published or accepted for publication. In some countries, doctoral students are increasingly being trained in cohorts, with the aim of providing a less isolating experience than that offered by the conventional supervisor–student relationship. PhD candidates are also encouraged to acquire transferable skills — for example, in data analysis, public engagement, project management or business, economics and finance. The value of such training would be even greater if these skills were to be formally assessed alongside a dissertation rather than seen as optional.

And yet, most PhDs are still assessed after the production of a final dissertation, according to a format that, at its core, has not changed for at least half a century, as speakers and delegates noted at an event in London last month on PhD assessment, organized by the Society for Research in Higher Educatio n. Innovations in assessment that are common at other levels of education are struggling to find their way into the conventional doctoral programme.

Take the concept of learning objectives. Intended to aid consistency, fairness and transparency, learning objectives are a summary of what a student is expected to know and how they will be assessed, and are given at the start of a course of study. Part of the ambition is also to help tutors to keep track of their students’ learning and take remedial action before it is too late.

PhD training is no longer fit for purpose — it needs reform now

Formative assessment is another practice that has yet to find its way into PhD assessment consistently. Here, a tutor evaluates a student’s progress at the mid-point of a course and gives feedback or guidance on what students need to do to improve ahead of their final, or summative, assessment. It is not that these methods are absent from modern PhDs; a conscientious supervisor will not leave candidates to sink or swim until the last day. But at many institutions, such approaches are not required of PhD supervisors.

Part of the difficulty is that PhD training is carried out in research departments by people who do not need to have teaching qualifications or awareness of innovations based on education research. Supervisors shouldn’t just be experts in their field, they should also know how best to convey that subject knowledge — along with knowledge of research methods — to their students.

It is probably not possible for universities to require all doctoral supervisors to have teaching qualifications. But there are smaller changes that can be made. At a minimum, doctoral supervisors should take the time to engage with the research that exists in the field of PhD education, and how it can apply to their interactions with students.

There can be no one-size-fits-all solution to improving how a PhD is assessed, because different subjects often have bespoke needs and practices ( P. Denicolo Qual. Assur. Educ. 11 , 84–91; 2003 ). But supervisors and representatives of individual subject communities must continue to discuss what is most appropriate for their disciplines.

All things considered, there is benefit to adopting a more structured approach to PhD assessment. It is high time that PhD education caught up with changes that are now mainstream at most other levels of education. That must start with a closer partnership between education researchers, PhD supervisors and organizers of doctoral-training programmes in universities. This partnership will benefit everyone — PhD supervisors and doctoral students coming into the research workforce, whether in universities or elsewhere.

Education and training in research has entered many secondary schools, along with undergraduate teaching, which is a good thing. In the spirit of mutual learning, research doctoral supervisors, too, will benefit by going back to school.

Nature 627 , 244 (2024)

doi: https://doi.org/10.1038/d41586-024-00718-0

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Understanding the role of gamma delta (γδ) T cells in pancreatic cancer metastasis

Lawrence, Mark (2022) Understanding the role of gamma delta (γδ) T cells in pancreatic cancer metastasis. PhD thesis, University of Glasgow.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a 1-year survival rate of 5.6% and a 10-year survival rate of <1%. In Scotland, 3 in 5 people with pancreatic cancer are diagnosed at late-stage metastatic disease, and surgical resection remains the only effective cure for patients with nonmetastatic disease. Given late-stage diagnosis and low rates of surgical resection, understanding the mechanisms of metastatic disease is of the utmost importance. In breast cancer, IL-17A+ gamma delta (γδ) T cells are potently prometastatic and drive myeloid cell expansion which impairs anti-metastatic CD8+ T cells. In PDAC, IL-17A has been implicated in early-stage PDAC progression, and γδ T cells have been shown to be abundant in human PDAC. Therefore, I sought to understand the role of γδ T cells in PDAC metastasis, and if they can promote metastasis in a similar manner as seen in breast cancer.

Using spontaneous KrasG12D;Trp53R172H;Pdx1-Cre (KPC) mice, I have phenotyped γδ T cells in mouse PDAC and assessed their role in PDAC tumourigenesis and metastasis. In short, IL-17A+ γδ T cells are significantly infiltrated into PDAC tumours, and Vγ6+ γδ T cells (considered IL-17A-producers) are expanded in KPC spleen. Crucially, the absence of γδ T cells in KPC mice leads to a two-fold reduction in the incidence of spontaneous liver metastasis. Contrasting with breast cancer, γδ T cells do not mediate crosstalk with neutrophils by systemic cytokine production, but instead communicate locally with tumour-associated macrophages within the PDAC TME. Furthermore, γδ T cells promote the expansion of the embryonic-derived (tissue-resident) macrophage compartment, which have greater pro-tumour function than monocyte-derived macrophages.

These results reveal that tumour-infiltrated γδ T cells in PDAC display a protumour phenotype, and that γδ T cells are indispensable for metastatic dissemination. They also reveal a novel phenotype where γδ T cells mediate crosstalk with macrophages specifically within the primary PDAC tumour. Further work is required to understand the mechanism of this crosstalk, but these findings may have important implications for the identification of future targets of anti-metastatic therapies.

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Emory primatologist Frans de Waal remembered for bringing apes ‘a little closer to humans’

Emory University | March 16, 2024

40 years of publishing : From "Chimpanzee Politics" in 1982 to "Different" in 2022.

Emory University primatologist Frans de Waal — who pioneered studies of animal cognition while also writing best-selling books that helped popularize the field around the globe — passed away March 14, 2024, from stomach cancer.

De Waal, Charles Howard Candler Professor Emeritus of Psychology and former director of the Living Links Center for the Advanced Study of Ape and Human Evolution at the Emory National Primate Research Center, was 75.

From his groundbreaking 1982 book “Chimpanzee Politics: Power and Sex Among Apes” to 2019’s “Mama’s Last Hug: Animal Emotions and What They Tell Us About Ourselves,” de Waal shattered long-held ideas about what it means to be an animal and a human.

“One thing that I’ve seen often in my career is claims of human uniqueness that fall away and are never heard from again,” de Waal said in 2014. “We always end up overestimating the complexity of what we do. That’s how you can sum up my career: I’ve brought apes a little closer to humans but I’ve also brought humans down a bit.”

“It’s difficult to sum up the enormity of Frans de Waal’s impact, both globally and here at Emory,” says Lynne Nygaard, chair of Emory’s Department of Psychology. “He was an extraordinarily deep thinker who could also think broadly, making insights that cut across disciplines. He was always ready to participate in an intellectual discussion.”

In addition to being a world-renowned scholar, beloved teacher and supportive colleague, “Frans was funny,” Nygaard says. “If a discussion became fraught, he could make just the right irreverent remark to get everyone to laugh and break the tension.”

“We may accept that we are descended from apes, but it takes the likes of Frans de Waal to remind us that we haven't traveled that far.” —TIME Magazine, Top 100 People who Shape Our World

Breaking taboos

George Romanes, a protégé of Charles Darwin, tried to connect ideas of animal consciousness and human consciousness in the late 1800s, but his theories were dismissed as anecdotal and anthropomorphic.

For nearly 100 years, the subject of the social mind of animals remained largely taboo in the scientific community. Finally, in 1976, neuroscientist Donald Griffin published his first edition of “The Question of Animal Awareness: Evolutionary Continuity of Mental Experience.” That book compiled observations suggesting animals might have thoughts worthy of exploring and that it was possible to do so in a scientifically objective way.

“Donald Griffin opened the door just a little bit and then Frans pushed it wide open. The rest is history,” says Harold Gouzoules, an Emory professor of psychology who studies primate social behavior and vocal communication.

Frans de Waal as a young scholar

De Waal wrote hundreds of peer-reviewed scientific articles comparing primate and human behavior. He demonstrated the roots of human nature in our closest living relatives through his studies of conflict resolution, reconciliation, cooperation, empathy, fairness, morality, social learning and culture in chimpanzees, bonobos and capuchin monkeys.

A prolific writer and editor, his impact reached far beyond academia through his articles for major magazines and newspapers and his 16 popular books that have been translated into 20 languages. He was a gifted speaker who wove deadpan humor into his many public talks — usually filled to capacity — about his research. His TED Talks have been viewed millions of times.

Animal emotions: In this Emory video, watch Frans de Waal discuss his 2019 book, "Mama's Last Hug."

Training the next generation

Through teaching and research projects, de Waal also helped train and influence many leaders in the field of animal cognition.

“Frans was a fantastic mentor, he really believed in his students,” says Sarah Brosnan, who received a PhD in 2004 in Emory’s Population Biology, Ecology and Evolution Program. Brosnan is now Distinguished University Professor of psychology at Georgia State University where she investigates the evolution of cooperation, decision-making and economic behavior among primates.

“Frans told us the best way to come up with research questions was to watch your animals and they will tell you what’s important,” recalls Brosnan.

She took his advice to heart.

One day, while Brosnan was feeding capuchin monkeys at the primate center, she tried to distract the dominant male, Ozzie, while she slipped peanuts to the others, to keep him from grabbing them all. Ozzie caught on, however, and brought Brosnan a piece of a naval orange from his enclosure, offering it in exchange for a peanut.

Oranges are generally a choice treat to monkeys, rating even higher than peanuts. “I wondered if the reason Ozzie was willing to trade a chunk of orange for a peanut was because everyone else was eating one,” she recalls.

A master of visualization

That simple question led to Brosnan and de Waal developing the famous cucumber-grape study on fairness.

Two capuchins were situated in enclosures next to one another. A researcher would ask them to do a task and if they succeeded give them a treat. The catch was one monkey was always rewarded with a piece of cucumber while the other monkey sometimes got a piece of cucumber and sometimes got a grape — a preferred treat among capuchin monkeys.

A video de Waal filmed of one of the experiments created a media sensation.

Unequal pay for equal work:  When the first monkey gives the researcher a rock, she is rewarded with a cucumber slice. But watch what happens when the first monkey sees the second monkey hand the researcher a rock — and get a much tastier grape instead.

A monkey that received only cucumber appears perfectly happy until she sees her companion receive a grape. Then her behavior changes. She accepts the next piece of cucumber only to throw it back at the researcher, pounding the surface in front of the enclosure and shaking its Plexiglas walls.

“That video struck home with a lot of people,” Brosnan says. “Who hasn’t felt like that monkey that’s only getting cucumbers? Our research showed something about the evolution of the sense of human fairness.”

De Waal, a skilled visual artist and photographer, routinely videotaped experiments — long before that became common practice in labs.

“Both Frans and I used the cucumber-grape experiment video in our TED Talks,” Brosnan notes. “Frans taught his students how to write well and how to give a good presentation. You weren’t allowed to just read some text. Your slides always had to have images and videos.”

Image captions

Animal reconciliation

Franciscus Bernardus Maria “Frans” de Waal was born in 1948 in s’Hertogenbosch, the Netherlands, where he trained as a zoologist and ethologist at three universities — Nijmegen, Groningen and Utrecht. In 1977 he received a PhD in biology from the University of Utrecht where Jan van Hooff, a Dutch biologist renowned for his research involving primates, was his mentor.

Frans de Waal as a young boy

For his dissertation, de Waal began working with the colony of chimpanzees at the Arnhem Zoo in the Netherlands. That work led to his first major discovery: chimpanzees make up after fights.

“I discovered that by just seeing how the opponents would come together after fights and kiss and embrace,” de Waal later said. “I never had trouble getting primatologists interested or convincing them, but other scientists were often skeptical. This meant conducting experiments and collecting data to convince them.”

Instead of describing the behavior he observed using a clinical term, such as “post-fight, affiliative contact,” de Waal called it reconciliation — a word, up until then, reserved for humans. This research became the basis of his book “Chimpanzee Politics,” which compared the schmoozing and scheming of chimpanzees involved in power struggles with that of human politicians.

“There really was no history of someone studying something as complex as reconciliation in animals,” says Kim Wallen, who recently retired as an Emory professor of psychology. “Frans faced a lot of challenges because he looked at questions that were outside the mainstream of animal behavior research. He persisted and carved out an area of his own.”

In 1981 de Waal moved to the United States to join the Wisconsin National Primate Research Center.

Wallen, who studied sex-related behaviors in humans and non-humans, recruited de Waal to join Emory in 1991. “His reputation preceded him,” Wallen recalls. “It was a big coup for Emory.”

Understanding our inner ape

At the field station of the Emory National Primate Research Center, de Waal kept a small office atop a tower. A windshield-like opening in the office overlooks a habitat where multi-generational groups of chimpanzees live outdoors.

De Waal supervised the construction of a building adjacent to the habitat for cognition research with the chimpanzees. A door would slide up allowing the chimpanzees to voluntarily come inside to try to solve a puzzle or perform a task.

A large part of de Waal’s research also encompassed bonobos, what he called “the forgotten ape,” including studies of bonobos in the San Diego Zoo and in the Democratic Republic of Congo. Both the chimpanzee and the bonobo are our genetic twins, but for 1.5% difference in DNA. And while chimpanzees rely on aggression to solve problems, the peaceable, sex-loving, female-dominated bonobos are so chill de Waal described them as “the hippies of the primate world.”

In his 2005 book, “The Inner Ape,” a New York Times Notable Book of the Year, he used these contrasting ape societies as the context to examine some of the most fundamental, complex and intense manifestations of human nature.

“We have an enormous spectrum of behavior, so don’t believe claims that we are inherently nasty, aggressive, selfish and uncooperative,” de Waal said in a 2006 interview. “My argument is that we have the potential to be everything we want to be. Our job is to bring out what we want.”

Making the most of every minute

In addition to his extreme productivity as a scientist, teacher and communicator, de Waal was a social animal, especially when it came to his students.

“I think Frans came across sometimes as reserved but he wasn’t like that once you got to know him,” Brosnan says. “He was so much fun. He would hold what he called ‘simian soirees’ at his house where graduate students would gather to talk. He was a fantastic piano player and he would play for us.”

De Waal retired from Emory in 2019 but remained active. He was in demand internationally and traveled widely, attending conferences and giving public talks. “The number of talks he would give in a year was always off-the-charts impressive,” Gouzoules said. “It was almost like a rock star touring around.”

De Waal also continued writing, publishing “Different: Gender Through the Eyes of a Primatologist” in 2022. In 2023, he made an appearance in New York for a public discussion with film icon Isabella Rossellini about the book, and what we may learn about sex and gender from primate studies.

Frans de Waal speaking at the Phil.Cologne international festival for philosophy in Germany in June 2023. (Photo by Ying Tang/NurPhoto via AP)

De Waal made his home in Stone Mountain, Georgia, where he lived with his wife of more than 40 years, Catherine Marin. The couple also maintained an apartment in the Netherlands where he had an affiliation with the University of Utrecht.

De Waal was made a Knight of the Order of the Netherlands Lion In 2010 and elected to the American Academy of Arts and Sciences in 2008 and the National Academy of Sciences in 2004. Among his many awards are the E.O. Wilson Literary Science Writing Award (2020), the Galileo Prize (2014), the Ig Nobel Prize (2012), Discover magazine’s “47 All-time Great Minds of Science” (2011), Time magazine’s 100 world’s most influential people (2007), the American Psychological Foundation Arthur W. Staats Award (2005) and the Los Angeles Times Book Award for “Peacemaking Among Primates” (1989).

Frans de Waal: Highlights from a career exploring animal and human behavior

1948: Born in s’Hertogenbosch, the Netherlands 1970s: Trained as a zoologist and ethologist at three Dutch universities (Nijmegen, Groningen and Utrecht) 1975: Began working with chimpanzees at the Arnhem Zoo (the Netherlands) 1977: Received PhD in biology from the University of Utrecht 1981: Joined the Wisconsin National Primate Research Center, focused on reconciliation behavior in monkeys  1982: Published first book, “ Chimpanzee Politics ,” which compared the schmoozing and scheming of chimpanzees involved in power struggles with that of human politicians 1984: Began working with bonobos (San Diego Zoo) and chimpanzees (Emory National Primate Research Center) 1989: Published “ Peacemaking Among Primates ” 1991: Joined Emory University’s Department of Psychology and National Primate Research Center, and began mentoring graduate students and post-doctoral fellows 1993: Elected to the Royal Dutch Academy of Sciences 1996: Published “ Good Natured: The Origins of Right and Wrong in Humans and Other Animals ” 1997: Published “ Bonobo: The Forgotten Ape ” 2001: Published “ The Ape and the Sushi Master: Cultural Reflections by a Primatologist ” 2004: Elected to the National Academy of Sciences 2005: Published “ Our Inner Ape .” Elected to the American Philosophical Society 2006: Published “ Primates and Philosophers: How Morality Evolved ” 2007: Named one of TIME magazine’s Top 100 People Who Shape Our World 2008: Elected Fellow of the American Academy of Arts & Sciences (AAAS) 2010: Knighted: Order of the Netherlands Lion. Published “ The Age of Empathy: Nature’s Lessons for a Kinder Society ” 2014: Published “ The Bonobo and the Atheist: In Search of Humanism Among the Primates ” 2016: Published “ Are We Smart Enough To Know How Smart Animals Are? ” 2019: Published “ Mama’s Last Hug: Animal Emotions and What They Tell Us About Ourselves .” Retired from Emory University.

2022: Published “ Different: Gender Through the Eyes of a Primatologist ”

Story by Carol Clark. Title center portrait photo by Catherine Marin. Other photos by Emory Photo/Video or courtesy unless noted. Design by Laura Douglas-Brown.

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5 Things To Know About Colon Cancer Prevention and Screening

Why colon cancer develops, listen to "5 things to know about colon cancer prevention and screening".

Colorectal cancer is the third most common cancer in the United States, and more than 150,000 people will be diagnosed with colorectal cancer this year. For Colon Cancer Awareness Month , Xavier Llor, MD, PhD, professor of medicine (digestive diseases) and director of the Gastrointestinal (GI) and Pancreatic Cancer Prevention Program , shared some things everyone should know about colorectal cancer.

1. Early-onset colorectal cancer is on the rise.

Over the last 40 years, there has been a decline in colon cancer overall; however, since 2011, there has been a very steady, significant increase year over year in colorectal cancers in younger individuals (under age 50). “We’re seeing a cohort effect, where everyone born from the early 1960s on carry a higher risk for colorectal cancers,” said Llor. “We’re seeing so many young people with healthy dietary habits, who don’t use tobacco, and who test negative for a genetic defect, and yet they have colon cancer at age 35. This trend is really worrisome.”

Researchers are still trying to understand why this trend is occurring. “It’s likely environmental factors, like the air we breathe or what we eat and drink. Genetics don’t change that fast,” said Llor. “This is the multi-million-dollar question in colon cancer prevention right now.”

2. Screening for average-risk patients now starts at age 45.

In response to the rise in colon cancer among younger people, the United States Preventative Services Task Force (USPTF) has endorsed screening for average-risk patients at age 45. Unfortunately, many younger adults are still not getting screened.

“Getting screened early could save your life,” Llor said.

Risk factors for colon cancer include lifestyle factors, like weight, diet, exercise, and substance use, along with genetic factors. People at higher risk of colon cancer should start screenings at age 40.

3. Patients with certain genetic diseases carry a higher risk of colon cancer

Research shows that approximately 5-6% of colorectal cancers are associated with a genetic factor. Yale’s Gastrointestinal (GI) and Pancreatic Cancer Prevention Program , which Llor co-leads, helps diagnose, screen, and coordinate care for patients with genetic syndromes that put them at higher risk for colorectal and other GI cancers.

“Navigating the healthcare system in this country is extremely complicated. It can be a huge burden for patients to manage different doctor visits and screenings, yet we know this kind of diligent follow-up is especially important for high-risk patients,” said Llor. “Our main goal is to provide the care coordination patients need to ease the burden for patients while comprehensively working with them to help them prevent cancer.”

Patients who may be at a higher risk for hereditary cancer include:

• A personal or family history of early-onset cancer (younger than 45-50 years)
• Multiple family members on the same side of the family with the same or related cancers
• An individual or family member with a diagnosis of more than one type of cancer
• A personal or family history of colorectal, endometrial, or breast cancer
• A personal or family history of ovarian or pancreatic cancer at any age
• A personal or family history of a rare type of cancer/tumor

4. There are multiple screening options for patients.

For many years, colonoscopies were thought of as the only colorectal cancer screening option. In recent years, organizations like the USPTF , American Cancer Society , and American Gastroenterological Association have encouraged the use of stool-based tests for certain patients.

“Now, clinicians can be smart about stratifying patients by risk and offering patients choices that work best for them,” said Llor. “Each test carries different benefits and risks. Ultimately, the best test is the one that gets done.”

Providers can now offer patients the choice between colonoscopies or stool-based tests. Each test carries different benefits and different risks.

To help providers determine which test is suitable for each patient, Yale developed a colon cancer screening pathway in Epic. The pathway provides health care providers with details about the sensitivities and risks of each screening option. It includes easy-to-share educational resources for patients so that they can understand the different screening options available to them. Providers can also order tests directly from the pathway.

5. Not all polyps become cancerous – but more research is needed

More than a third of patients over 50 who have a colonoscopy will have polyps, which are abnormal growths on the inner walls of the colon or rectum. A very small percentage of polyps progress into cancer.

“We still don’t understand which polyps will progress into cancer or why, and only in the case of the advanced ones do we have a high level of certainty they can progress to cancer,” said Llor. He and his colleagues are part of a multi-site study funded by the National Cancer Institute that is looking into this question. Specifically, the research aims to understand if a patient with one or two small tubular adenomas (a specific type of polyp) has a higher risk of colon cancer. Current guidelines recommend more frequent colonoscopies for patients with this finding. This research may help understand if these more frequent screenings are necessary for patients.

Since forming one of the nation’s first sections of hepatology more than 75 years ago and then gastroenterology nearly 70 years ago, Yale School of Medicine’s Section of Digestive Diseases has had an enduring impact on research and clinical care in gastrointestinal and liver disorders. To learn more about their work, visit Internal Medicine: Digestive Diseases .

Featured in this article

• Xavier Llor, MD, PhD Professor of Medicine; Director, GI and Pancreatic Cancer Prevention Program, Digestive Diseases