Pancreatic Cancer: Basic Mechanisms and Therapies

1st Edition, Volume 159 - May 31, 2023
Editors: Luni Emdad, Azeddine Atfi, Rajan Gogna, Jose G Trevino, Paul B. Fisher
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 5 4 - 1
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 5 5 - 8

Pancreatic Cancer: Basic Mechanisms and Therapies, Volume 159 in the Advances in Cancer Research, presents the latest release in this ongoing, well-regarded serial with in… Read more

Purchase options

LIMITED OFFER

Save 50% on book bundles

Immediately download your ebook while waiting for your print delivery. No promo code is needed.

Institutional subscription on ScienceDirect

Request a sales quote

Pancreatic Cancer: Basic Mechanisms and Therapies, Volume 159 in the Advances in Cancer Research, presents the latest release in this ongoing, well-regarded serial with invaluable information on the exciting and fast-moving field of cancer research.

Pancreatic cancer (PC) is the third leading cause of cancer-related deaths in the United States. Greater than 90% PCs are Pancreatic ductal adenocarcinomas (PDAC) 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. In the clinic, the PDAC patients often present with incurable disease at the time of first diagnosis. This cancer is particularly lethal because of its propensity to spread quickly 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. 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 issue, we have included ten review articles by experts that cover cancer disparities, PDAC pathobiology, the roles of the tumor microenvironment, tumor heterogeneity, PC stem cells, genetic and signaling events critical for PDAC pathogenesis, Immunotherapy and chemoresistance in PDAC, and different PDAC mouse models. This special issue highlights recent research progress in PDAC, which bridges the gap between basic and clinical research.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter One: Notch signaling pathway in pancreatic tumorigenesis
Abstract
1: Introduction
2: Roles of Notch signaling in pancreatic ductal adenocarcinoma (PDAC)
3: Roles of Notch signaling in pancreatic neuroendocrine tumor (PNET)
4: Perspective
References
Chapter Two: Deciphering epithelial-to-mesenchymal transition in pancreatic cancer
Abstract
Highlights
1: Significance
2: Introduction
3: Defining EMT and its molecular mechanisms and pathways
4: The role of EMT in promoting tumor development and metastasis
5: EMT influences the initiation, survival, and metastasis of pancreatic cancer
6: EMT as a therapeutic target for PDAC
7: Perspectives, challenges and future directions
References
Chapter Three: In vivo models of pancreatic ductal adenocarcinoma
Abstract
1: Introduction
2: Spontaneous tumor models
3: Implantation models
4: Conclusions
Acknowledgments/Funding
References
Chapter Four: Interplay between MAP kinases and tumor microenvironment: Opportunity for immunotherapy in pancreatic cancer
Abstract
1: Introduction
2: Current treatments and drug resistance in pancreatic cancer
3: Pancreatic cancer TME and drug resistance
4: Expression and function of ICPs in pancreatic cancer
5: MAP4K → MAP3K → MAP2K → MAPK signaling module in pancreatic cancer
6: Targeting ICPs and MAPKs in pancreatic cancer
7: Summary
References
Chapter Five: Targeting KRAS in pancreatic cancer: Emerging therapeutic strategies
Abstract
1: Introduction
2: Biochemistry of KRAS
3: KRAS signaling pathways
4: KRAS mutations in PC
5: Emerging KRAS-targeted therapies
6: KRAS-targeted combination strategies
7: KRAS and cellular senescence
8: Challenges for effectively targeting KRAS in PC
9: Future perspectives and conclusions
References
Chapter Six: Racial disparities in pancreatic cancer clinical trials: Defining the problem and identifying solutions
Abstract
1: Introduction
2: Racial implicit bias as a barrier to enrollment
3: Access to trials and study design barriers
4: Impediments to clinical trial recruitment
5: Increasing pancreatic cancer trial diversity—A way forward
References
Chapter Seven: Tumor heterogeneity: An oncogenic driver of PDAC progression and therapy resistance under stress conditions
Abstract
1: Introduction
2: PDAC tumoral heterogeneity
3: PDAC adapts to grow in stress conditions
4: PDAC therapeutic options
5: Tumor heterogeneity contributes to treatment resistance
6: Conclusion
Acknowledgments
References
Chapter Eight: Oncogenic signaling pathways in pancreatic ductal adenocarcinoma
Abstract
1: Introduction
2: Oncogenic signaling pathways in PDAC
3: MYC: Master regulator of PDAC aggressiveness
4: Elucidation of PDAC heterogeneity through single cell genomic approaches
5: Conclusions and future directions
Acknowledgments
References
Chapter Nine: Chemoresistance in pancreatic ductal adenocarcinoma: Overcoming resistance to therapy
Abstract
1: Introduction
2: PDAC treatment strategies and chemoresistance
3: Methods to predict PDAC chemoresistance
4: Role of EMT in PDAC chemoresistance
5: Role of non-coding RNAs in PDAC chemoresistance
6: Role of the microenvironment in PDAC chemoresistance
7: Role of nucleoside transporters in PDAC chemoresistance
8: Role of autophagy in PDAC chemoresistance
9: Role of metabolism in PDAC chemoresistance
10: Role of extracellular vesicles (EV) and exosomes in PDAC chemoresistance
11: Role of signaling pathways in PDAC chemoresistance
12: Role of pancreatic tumor microbiome in PDAC chemoresistance
13: Future directions: Methods to sensitize pancreatic cancer to therapy
References
Chapter Ten: Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma
Abstract
1: Introduction
2: Clinical issues in pancreatic ductal adenocarcinoma
3: Cancer stem cells in pancreatic ductal adenocarcinoma
4: Tumor microenvironment in pancreatic cancer
5: Metastasis in pancreatic ductal adenocarcinoma
6: Conclusion
Acknowledgments
References

Luni Emdad

Luni Emdad, PhD, MBBS received her PhD degree in Medical Science from the Nagoya University Graduate School of Medicine and her Bachelor degree in Medicine and Surgery (MBBS) from Dhaka Medical college. After completing her Postdoctoral training in the department of Pathology and Urology with Dr. Paul B. Fisher at the Columbia University, she remained as Associate Research Scientist at the Columbia University until Dec 2007. From 2008-2011, she served as Assistant Professor, Department of Neurosurgery, Mount Sinai School of Medicine, New York. In 2011, she joined the Department of Human and Molecular Genetics, Virginia Commonwealth University as an Assistant professor. In 2020, she was promoted to Associate professor at Virginia Commonwealth University. Dr. Emdad is a scientist with a clinical background (dual degree of Bachelors of Medicine and Surgery and Ph.D.) and has a longstanding research experience in cancer research with in depth molecular knowledge in targeted experimental therapeutics development for cancer. She has published over 150 in journals such as Proceedings of the National Academy of Science USA, Cancer Research, Journal of Clinical Investigation, Hepatology, Oncogene, Semin Cancer Biol, Neuro-Oncology and so on. She has served as principal investigator in two sponsored research programs and an inventor in two issued US patents.

Affiliations and expertise

Associate Professor of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

Azeddine Atfi

Dr. Azeddine Atfi is the leader of Cancer Biology Program at NCI-designated Massey Cancer Center. He is also the Professor and Chair of the Cellular and Molecular Pathogenesis Division at the Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA.

Affiliations and expertise

Cancer Biology Program, NCI-designated Massey Cancer Center; Cellular and Molecular Pathogenesis Division at the Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA

Rajan Gogna

Dr. Rajan Gogna is an assistant professor at the School of Medicine Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.

Affiliations and expertise

School of Medicine Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

Jose G Trevino

Dr. Jose Trevino is an associate professor at the Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA.

Affiliations and expertise

Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA

Paul B. Fisher

Paul B. Fisher, MPh, PhD, FNAI, Professor and Chairman, Department of Human and Molecular Genetics, Director, VCU Institute of Molecular Medicine Thelma Newmeyer Corman Chair in Cancer Research in the VCU Massey Cancer Center, VCU, School of Medicine, Richmond, VA, and Emeritus Professor, Columbia University, College of Physicians & Surgeons, New York, NY. Dr. Fisher is among the top 10% of NIH funded investigators over the past 35-years, published approximately 625 papers and reviews, and has 55 issued patents. He pioneered novel gene/discovery approaches (subtraction hybridization), developed innovative therapeutic approaches (Cancer Terminator Viruses), presented numerous named and distinguished lectures, founded several start-up companies, was Virginia Outstanding Scientist of 2014 and elected to the National Academy of Inventors in 2018. Dr. Fisher is a prominent nationally and internationally recognized cancer research scientist focusing on understanding the molecular and biochemical basis of cancer development and progression to metastasis and using this garnered information to develop innovative approaches for diagnosing and treating cancer. He discovered and patented novel genes and gene promoters relevant to cancer growth control, differentiation and apoptosis. His discoveries include the first cloning of p21 (CDK inhibitor), human polynucleotide phosphorylase, mda-9/syntenin (a pro-metastatic gene), mda-5 and mda-7/IL-24, which has shown promising clinical activity in Phase I/II clinical trials in patients with advanced cancers. Dr. Fisher alsohas a documented track record as a successful seasoned entrepreneur. He was Founder and Director of GenQuest Incorporated, a functional genomics company, which merged with Corixa Corporation in 1998, traded on NASDAQ and was acquired by GlaxoSmithKline in 2006. He discovered the cancer-specific PEG-Prom, which is the core technology of Cancer Targeting Systems (CTS, Inc.), a Virginia/Maryland-based company (at Johns Hopkins Medical Center) focusing on imaging and therapy (“theranostics”) of metastatic cancer (2014) by Drs. Fisher and Martin G. Pomper. He co-founded InVaMet Therapeutics (IVMT) and InterLeukin Combinatorial Therapies (ILCT) with Dr. Webster K. Cavenee (UCSD) (2017/2018).

Affiliations and expertise

Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Virginia, USA