Role Of Transcription Factors In Gastrointestinal Malignancies

This book illustrates the importance of transcription factors in gastrointestinal cancer progression and metastasis with regard to understanding the mechanism and target definition in drug discovery. Further, it describes the complex issues associated with cancer cell growth and metastasis. The respective chapters provide detailed information on the various types of transcription factors (NF-kB, HIF-1, STAT-3, E2F1, and Sp1) and gastric-associated cancers (esophagus, stomach, colorectal, liver and pancreatic cancers) in connection with specific functional studies like cell cycle, angiogenesis, migration, invasion and apoptosis. These transcription factors control the expression of several signaling pathways involved in tumor growth, making them ideal targets for gastrointestinal cancer therapy. In closing, the book provides comprehensive descriptions of the major challenges associated with gastrointestinal cancer therapy.

This book provides an up-to-date overview of gastrointestinal malignancies, including prevention, early detection, intervention, and life-extending therapeutics. It also assesses various biomarkers used for diagnostics, prognostics and prediction of response to chemoresistance. Further, it discusses the latest trends in the use of small-molecule targeted therapies and immunotherapies as single agents or combination with other treatments. Since resistance to radiation and chemotherapy contribute to the high recurrence and poor survival rates, improving the outcome for GI malignancies is dependent on the introduction of new biomarkers and therapeutic agents. Lastly, the book systematically investigates novel theranostics approaches using nanotechnology for the detection, diagnosis, and personalized treatment of GI malignancies.

This book describes various novel biomarkers for the early diagnosis of gastrointestinal (GI) cancers. It also highlights recent advances in understanding the role of molecular markers and biomarkers, such as volatile biomarkers, serum biomarkers, predictive and prognostic molecular markers for the early detection of GI cancers. Further, it discusses novel biomarkers, including circulating microRNAs, serum microRNA and plasma microRNA in GI cancer. The book presents breakthrough technologies like ultra-sensitive nano-chips, nanosensors, nanodevices, biosensors, electrochemical biosensors, optical biosensors, DNA biosensors, synthetic biology devices, and 'omics' technologies for the early diagnosis of gastrointestinal cancer. In addition it examines the potential of genome-wide association studies, big data analytics, computation biology, systems biology, and nanotechnology for early diagnostics and therapeutics for gastrointestinal cancer, with a focus on personalized cancer treatment. The book is a valuable source for researchers and clinicians engaged in detection and diagnosis of gastrointestinal cancers.

Gastrointestinal (GI) malignancies account for a large portion of cancers worldwide. Although incidence of esophageal, gastric, and colorectal cancers has decreased in recent years, pancreatic and liver cancer have increased. The mainstay of GI cancer therapy is chemoradiation and surgery. Despite significant medical advancements, diagnosis and therapy for GI cancers remain challenging due to tumor cell resistance to chemoradiotherapy. The tumor’s increased cell signalling due to excessive transcription factor activation and increased stellate cell activity leads to collagen deposition formation of a dense stroma around the tumor, which prevents drugs from reaching the malignant cells. This leads to tumor chemoresistance. To circumvent these difficulties, drug therapy targeting the tumor’s specific microenvironment and the additive anticancer effect of phytochemicals can allow for more effective treatment. This volume will be the first on the market on the topic of phytochemicals and their effect on the tumor microenvironment (TME). TME is an emerging area of research and the book will be a welcome introductory addition to the field.

The aim of this book is to provide comprehensive overview of the role of different tyrosine kinases in the progression and metastasis of various cancers of the gastrointestinal tract such as esophagus, liver, pancreas, stomach, and colorectal. Activation of various signaling pathways and tyrosine kinases are responsible for resistance to chemo and radiotherapy in these gastrointestinal malignancies. Targeting these tyrosine kinases, which regulate the activities of survival pathways in growth, and metastasis is a rational strategy in gastrointestinal cancer therapy. Each chapter embedded in this book covers information pertaining to a specific tyrosine kinase and its impact on various malignancies, which is not only significant for basic and clinical research investigations but will also be valued by students at advanced undergraduate to postgraduate levels.

An Innovative Approach to Studying and Treating Cancer: Targeting pH describes one of the few characteristics of cancer that is not shared by normal tissues: the reversal or inversion of the pH gradient when intracellular pH becomes alkaline and extracellular pH becomes acid. This is now recognized as one of the most selective and differential hallmarks of all cancer cells and tissues, being the opposite of the condition found in normal tissues and a potential target in order to achieve either a stable disease or even regression with no toxicity. The book discusses topics such as lactic acid and its transport system in the pH paradigm, mechanisms to decrease extra cellular pH and increase intracellular pH, NHE-1 activity in cancer, carbonic anhydrases, vacuolar ATPase proton pump, and the sodium-bicarbonate cotransporter system. Additionally, it discusses complementary pharmacological interventions, cellular acidification and extracellular alkalinization as a new and integral approach to cancer treatment. Analyzes the mechanisms that lead to the inversion of pH gradient in cancer tissues Summarizes almost 100 years of research on pH inversion in cancer in one single source, discussing the most relevant and updated researches in the field Proposes new efficient treatments against cancer using pH inversion mechanisms, either with new drugs like proton transport inhibitors and proton pump inhibitors (PTIs and PPIs) or with repurposed drugs

Gastrointestinal malignancies encompass a large number of tumor types, and collectively are responsible for a significant portion of new cancer cases annually. According to the IARC database, colorectal cancer alone is responsible for approximately 10% of new cases of cancer worldwide annually. There is significant heterogeneity across the various tumor types, with different pathways and factors involved in oncogenesis, as well as varying degrees of prognosis depending on the tumor type. Non-coding RNAs (ncRNAs) contribute to a significant portion of the human transcriptome, and of particular interest are the micro-RNAs (miRNAs), long ncRNAs (lncRNAs), and circular ncRNAs (circRNAs). With the advent of next-generation sequencing and new technologies such a minimally invasive biopsy techniques, there is a growing body of evidence elucidating the role of ncRNAs in the progression of various form of gastrointestinal cancers. Furthermore, in addition to their relevance to cancer progression, these ncRNAs have important potential as biomarkers and prognostic markers for various GI cancers.

This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.