Immune Landscape Of Pancreatic Cancer Development And Drug Resistance

Immune landscape of pancreatic cancer development and drug resistance explores the advances in immune-based therapies aimed at harnessing the power of the immune system against pancreatic cancer and rewiring tumor microenvironments to eradicate pancreatic cells. With a strong focus on the development of therapeutic methods to improve the survival rates of pancreatic cancer, this book also shows the latest trends in immune targeted approaches for pancreatic cancer treatment. In 12 chapters Immune landscape of pancreatic cancer development and drug resistance discusses the current understanding of PC development and its various mutational and immune features and explore some of the new immune-based therapies aimed at targeting pancreatic cancer. It covers the urgent need for developing novel therapeutic modalities and aims at delineating future fields and avenues of research in pancreatic cancer treatment. The book provides the reader with an updated understanding of the immune landscape of PC and an all-encompassing overview of the latest trends in immune targeted approaches for PC treatment. This book is a valuable resource for health professionals, scientists and researchers, students, and all those who wish to broaden their knowledge of the advances in immunotherapy in pancreatic cancer. Summarizes the potential combination strategies and latest clinical trials in pancreatic cancer Provides an in-depth overview of our current understanding of pancreatic cancer development, including its mutational and immune features Explores some of the new immune-based therapies aimed at targeting PC Shows pancreatic cancer progression and basic elements in tumor microenvironments and their role in PC progression, also covering immunotherapy strategies

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. The recent overview of Racial Disparities in Pancreatic Cancer Clinical Trials; Overview the evolution of in vivo models for PDAC Up-to-date discussion of diverse genetic and molecular signaling changes in PDAC; Role of tumor heterogeneity in therapy resistance in PDAC; Chemoresistance in PDAC and how to overcome this challenge; Current and emerging approaches and strategies for advancing targeted therapy and immunotherapy for PDAC New insights into the role of epithelial-to-mesenchymal transition, tumor microenvironment (TME) and interactions of TME with cancer stem cells in PDAC pathogenesis, progression and therapeutic resistance

Theranostic Approach for Pancreatic Cancer modulates the biologic properties of stroma in pancreatic cancer by targeting the several chemotherapy resistance mechanisms to impede their malignant property through introducing new strategies and drugs for tackling the disease. It brings information about ongoing research as well as clinical data about pancreatic cancer and provides detailed descriptions about diagnostic and therapeutic options for easy understanding. The book discusses several topics related to pancreatic cancer, such as stem cells, drug resistance and pancreatic tumor microenvironment, the latest developments in chemotherapy for metastatic cancer and chemoprevention, and epigenome as a therapeutic strategy. Additionally, it encompasses a discussion on theranostic clinical applications for personalized treatment and management of pancreatic cancer. The book is a valuable resource for cancer researchers, oncologists, and several members of the biomedical field who need to understand more about the diagnosis and treatment of pancreatic cancer. Provides information on the roadblocks of chemotherapy in patients with newly diagnosed and metastatic pancreatic cancer“/li> Discusses treatment options available currently and prospective options for the future Focuses especially on stroma, tumor microenvironment, stem cells, stellate cells, transcription factors, growth factors, and important signaling pathways as already tested types of treatment

Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy edited by Dr. Nagaraju, PhD., DSc. focuses on overriding the resistance from chemotherapeutic drugs with a broader range of treatment options. It particularly focuses on stroma, tumor microenvironment, stem cells, stellate cells, transcription factors, growth factors, and important signaling pathways. This volume discusses topics such as pancreatic cancer biology, current therapeutic options, EMT, chemotherapy resistance mechanisms, and genetic manipulations and natural products to enhance the sensitivity of pancreatic cancer to chemotherapy. Additionally, it discusses small targeted molecules and pancreatic cancer trials, and nanotechnology-based drug delivery. Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy is a valuable source for researchers and advanced students in cancer and oncology as well as clinicians and medical students who are interested in learning more about ways to break pancreatic cancer resistance to chemotherapy. Modulates the biologic properties of stroma in pancreatic cancer by targeting the several chemotherapy resistance mechanisms to impede their malignant property by introducing new strategies and drugs Provides information about on-going research as well as clinical data on pancreatic cancer and detailed descriptions about therapeutic options for easy understanding Utilizes full color figures to help the understanding of the content and tables for easy comparison of information as well as quick access to it

Pancreatic cancer is a challenging and complex disease characterized by a dense fibrotic stroma and an immunosuppressive tumor microenvironment. Until recently, there were no predictive biomarkers to personalize selection of targeted or biologic therapies as a part of standard of care treatment. Moreover, the regulatory immune population of cells creates a “cold”, non-immunogenic tumor that is resistant to immunotherapies including checkpoint inhibitors. However, in the last few years, there has been substantial progress in our understanding of the role mutations in the pathogenesis of disease leading to increased adoption of germline and next generation sequencing to identify mutations and fusions to optimize selection of therapies and select patients for clinical trials of targeted agents. This book provides a comprehensive, global overview on therapy for pancreatic cancer, exploring approved therapies and focusing on the “Next” in drug development including molecularly targeted therapy and efforts at “Drugging the Undruggable”: the KRAS mutation. It also addresses efforts at targeting the inhospitable stroma to improve drug delivery to the tumor cells, incorporating ct DNA (liquid biopsies) in the care of patients and recent advances in immunotherapy. Pancreatic Cancer: Current Therapeutics and Future Directions will illuminate these challenges, review existing therapeutics, and highlight current and future efforts to improve outcomes in this devastating disease. Useful to physicians, fellows, medical students, residents, physician assistants, nurse practitioners, pharmaceutical companies and researchers interested in pancreatic cancer, it will first explain management of localized disease including resectability and adjuvant and neoadjuvant therapies. Targeted therapies including molecular, immunotherapy, stroma and role of ctDNA or “liquid biopsies” will be addressed. Finally, the book will explore the important role of pain management, diet and exercise in improving outcomes in pancreatic cancer.

"Purpose: Pancreatic Ductal Adenocarcinoma (PDAC) is highly chemo-resistant with a 5-year survival rate of less than 10%. Although the microenvironment of PDAC is generally immunosuppressive, the rare and hypermutated mismatch repair (MMR) deficient (MMR-d) PDAC subtype is sensitive to immune check point inhibitors (ICIs). The more prevalent homologous recombination (HR) deficient (HR-d) PDAC subtype may also harbor immunogenicity amenable to treatment with ICIs. To investigate the actionability of HR-d PDAC with ICIs, I compared the immune landscapes of HR-d versus HR/MMR-intact PDAC by evaluating a molecularly annotated retrospective case series. Experimental Design: Germline genetic testing and tumor molecular hallmarks were used to classify 192 PDAC cases as HR/MMR-intact (n=166), HR-d (n=25) or MMR-d (n=1). The cases were immunostained for CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), CD68+ tumor-associated macrophages (TAMs) and PD-L1. To distinguish immune cells infiltrating the tumor versus those surrounding the perimeter, immune cells located within 10 uM of a tumor cell cluster perimeter were classified intra-tumoral. Immune cells mapping 10 to 50 uM from a tumor cell cluster perimeter were considered peri-tumoral, while immune cells located beyond 50 uM from a tumor cell cluster perimeter were classified as stromal. Using these spatial distribution definitions, I analyze the immune landscape of HR-d versus HR/MMR-intact PDAC. I also evaluated the immunohistochemical positivity of programmed death-ligand 1 (PD-L1) across the subgroups. Results: The HR-d group showed significantly longer median overall survival compared to the HR/MMR-intact group (29.1 months versus 19.9 months, p

This book provides the reader with an overall understanding of the biology of pancreatic cancer, hereditary, complex signaling pathways and alternative therapies. The book explains nutrigenomics and epigenetics mechanisms such as DNA methylation, which may explain the etiology or progression of pancreatic cancer. Book also summarizes the molecular control of oncogenic pathways such as K-Ras and KLF4. Since pancreatic cancer metastasizes to vital organs resulting in poor prognosis, special emphasis is given to the mechanism of tumor cell invasion and metastasis. Role of nitric oxide and Syk kinase in tumor metastasis is discussed in detail. Prevention strategies for pancreatic cancer are also described. The molecular mechanisms of the anti-cancer effects of curcumin, benzyl isothiocyante and vitamin D are discussed in detail. Furthermore, this book covers the basic mechanisms of resistance of pancreatic cancer to chemotherapy drugs such as gemcitabine and 5-flourouracil.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Principles of Immunotherapy in Breast and Gastrointestinal Cancers: Activity, Mechanisms of Resistance and New Sensitization Strategies presents updated research findings on immunotherapy, with special focus on the mechanisms of resistance of those cancer types and how to overcome them. The book discusses topics such as tumor cell-intrinsic and extrinsic mechanisms of cancer resistance to immunotherapy; the role of currently available biomarkers; strategies to overcome therapeutic resistance; sensitizing agents for cancer resistance to cell mediated immunotherapy; and Immunotherapeutic approaches, mechanisms of resistance and sensitizing strategies in gastroesophageal and biliopancreatic tumors and colorectal cancer. It is a valuable resource for researchers, students and members of the biomedical and medical fields who want to learn more about resistance to immunotherapy and how to overcome it. Presents relevant findings on immunotherapy for breast and GI cancer types in a synthetic and didactic way for easy consult Describes resistance mechanisms of those cancer types and how to overcome them to improve immunotherapy outcomes Encompasses several diagrams and figures to help readers get a clearer picture of the research findings and how they can be applied to the clinical setting

In addition to the extensive discussion, illustrations, and up-to-date referencing of the numerous pancreatic tumours and tumour-like lesions, normal gross, histologic and cytologic findings, and on pancreatic tumour staging are covered. These discussions complement the treatment of the issue of frozen section interpretation, dissection, and reporting of pancreatic resection specimens.