Pancreatic Cancer: Basic Mechanisms and Therapies

Pancreatic cancer continues to challenge patients, clinicians, and scientists. Recent discoveries and technical advances instill optimism that hopefully, in the not-too-distant future, additional improved diagnostic and therapeutic approaches to treating this aggressive disease will become available. This topic was recently covered in a thematic volume of Advances in Cancer Research edited by VCU and VIMM members Drs. Emdad, Atfi, Gogna, Trevino and Fisher. This special issue highlights the recent research progress in pancreatic cancer, which bridges the gap between basic and clinical research. Accordingly, this volume of ACR will be of interest to both undergraduate and graduate students, postdoctoral scientists, basic research scientists, medical students, and clinicians.

Preface for Volume

Pancreatic cancer (PC) is the third leading cause of cancer-related deaths in the United States. More than 90% PCs are pancreatic ductal adenocarcinomas (PDACs), which have a dismal estimated 5-year overall survival of only 11%. PDAC is predicted to become the second leading cause of mortality in the United States by 2030. Its aggressive nature and resistance to conventional and targeted therapeutic agents often leads to a clinical presentation of incurable disease at the time of diagnosis. This cancer is particularly lethal because of its propensity to quickly spread to distant organs, including the lymphatic system. PDAC metastasis occurs shortly after tumor initiation and is caused by a complex interaction between autonomous tumor cells and cellular elements of the tumor microenvironment (TME). Although PDAC remains a challenging disease to treat and a leading cause of cancer-related deaths, progress is being made in disease etiology and pathogenesis, and intensive research is focused on developing optimal treatment approaches for patients. Considering the continuous progress being made in understanding PDAC pathogenesis and designing new therapies, it was considered timely to develop an up-to-date thematic issue of Advances in Cancer Research (ACR) focused on PDAC.

In this thematic volume of Advances in Cancer Research entitled “Pancreatic Cancer: Basic Mechanisms and Therapies,” the editors included 10 review chapters by experts, which cover cancer disparities, PDAC pathobiology, the roles of the TME, tumor heterogeneity, PC stem cells, genetic and signaling events critical for PDAC pathogenesis, immunotherapy and chemoresistance in PDAC, and different PDAC mouse models. The editors believe that the current thematic issue of ACR, which focuses on PDAC, will serve as a timely and imperative reference source for faculty, researchers, clinicians, and students and will also be of significant value to the readership of ACR.

Chapters in this Volume:

Chapter One - Notch signaling pathway in pancreatic tumorigenesis by Wen-Cheng Chung and Keli Xu

Chapter Two - Deciphering epithelial-to-mesenchymal transition in pancreatic cancer by Creighton Friend, Parash Parajuli, Mohammed S. Razzaque, and Azeddine Atfi

Chapter Three - In vivo models of pancreatic ductal adenocarcinoma by Vignesh Vudatha, Kelly M. Herremans, Devon C. Freudenberger, Christopher Liu, and Jose G. Trevino

Chapter Four - Interplay between MAP kinases and tumor microenvironment: Opportunity for immunotherapy in pancreatic cancer by Sandeep Kumar, Sunil Kumar Singh, Piush Srivastava, Swathi Suresh, Basabi Rana, and Ajay Rana

Chapter Five - Targeting KRAS in pancreatic cancer: Emerging therapeutic strategies by Sajid Khan, Vivekananda Budamagunta, and Daohong Zhou

Chapter Six - Racial disparities in pancreatic cancer clinical trials: Defining the problem and identifying solutions by Allison N. Martin and Rebecca A. Snyder

Chapter Seven - Tumor heterogeneity: An oncogenic driver of PDAC progression and therapy resistance under stress conditions by António M. Palma, Vignesh Vudatha, Maria Leonor Peixoto, and

Esha Madan

Chapter Eight - Oncogenic signaling pathways in pancreatic ductal adenocarcinoma by Rahul Agrawal and Kedar Nath Natarajan

Chapter Nine - Chemoresistance in pancreatic ductal adenocarcinoma: Overcoming resistance to therapy by Praveen Bhoopathi, Padmanabhan Mannangatti, Swadesh K. Das, Paul B. Fisher, and Luni Emdad

Chapter Ten - Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma by António M. Palma, Grace G. Bushnell, Max S. Wicha, and Rajan Gogna

Funding Sources

The editors would like to recognize support from the following sources: National Cancer Institute (R01CA242003 to J.G.T., U54CA233444 to J.G.T., and U54CA233444-03S1 to J.G.T.), and the Joseph and Ann Matella Fund for Pancreatic Cancer Research ( J.G.T.); NIH/NCI R01 CA259599 (P.B.F., Xiang-Yang (Shawn) Wang), NIH/NCI R01 CA244993 (Devanand Sarkar, P.B.F.), the National Foundation for Cancer Research (NFCR) (P.B.F.), the Human and Molecular Genetics Development Fund (L.E., SKD), the VCU Institute of Molecular Medicine (P.B.F.), and a sponsored research agreement with InVaMet Therapeutics (IVMT) (SKD). NIH-NCI Cancer Center Support Grant P30 CA016059; Fundac¸a˜o para a Ci^encia e a Tecnologia Grant 2020.05319.BD to A.M.P., SNSF, Swiss Cancer League, LB692, FCT LB506, the VCU Massey Cancer Center core grant (R.G.).

Publications:

Emdad L, Atfi A, Gogna R, Trevino JG, Fisher PB. (Eds.). Pancreatic Cancer: Basic Mechanisms and Therapies. Adv Cancer Res. 2023;159:xiii-xviii. PMID: 37268403. DOI: 10.1016/S0065-230X(23)00049-0

Bhoopathi P, Mannangatti P, Das SK, Fisher PB, Emdad L. Chemoresistance in pancreatic ductal adenocarcinoma: Overcoming resistance to therapy. Adv Cancer Res. 2023;159:285-341. PMID: 37268399. DOI: 10.1016/bs.acr.2023.02.010

Friend C, Parajuli P, Razzaque MS, Atfi A. Deciphering epithelial-to-mesenchymal transition in pancreatic cancer. Adv Cancer Res. 2023;159:37-73. PMID: 37268401. DOI: 10.1016/bs.acr.2023.02.008

Palma AM, Bushnell GG, Wicha MS, Gogna R. Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma. Adv Cancer Res. 2023;159:343-372. PMID: 37268400. DOI: 10.1016/bs.acr.2023.02.007

Vudatha V, Herremans KM, Freudenberger DC, Liu C, Trevino JG. In vivo models of pancreatic ductal adenocarcinoma. Adv Cancer Res. 2023;159:75-112. PMID: 37268402. DOI: 10.1016/bs.acr.2023.02.002

About the Investigators:

Luni Emdad is Associate Professor of Human and Molecule Genetics, and a member of the VIMM, VCU SOM. Azeddine Atfi is Professor of Biochemistry and Molecular Biology, and a member of the VIMM and VCU Massey Cancer Center VCU SOM. Rajan Gogna is Assistant Professor of Human and Molecule Genetics, and a member of the VIMM and VCU Massey Cancer Center VCU SOM. Jose G. Trevino is Chair of the Division of Surgical Oncology at the VCU SOM and Surgeon-in-Chief at VCU Massey Cancer Center. Paul B. Fisher, MPh, PhD, FNAI, is Professor of Human and Molecular Genetics HMG, Director of the VCU Institute of Molecular Medicine VIMM and Thelma Newmeyer Corman Chair in Cancer Research in the VCU MCC, VCU SOM.