The P53 Protein


Book Description

Decades of research on the tumor suppressor p53 have revealed that it plays a significant role as a "guardian of the genome," protecting cells against genotoxic stress. In recent years, p53 research has begun to move into the clinic in attempts to understand how p53 is frequently inactivated in-and sometimes even promotes-human cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the rapid progress that has recently been made in basic and clinical research on p53. The contributors review new observations about its basic biology, providing updates on the functions of its isoforms and domains, the myriad stresses and signals that trigger its activation or repression, and its downstream effects on genome stability and the cell cycle that enforce tumor suppression in different cell and tissue types. They also discuss how p53 dysfunction contributes to cancer, exploring the various inherited and somatic mutations in the human TP53 gene, the impact of mutant p53 proteins on tumorigenesis, and the prognostic value and clinical outcomes of these mutations. Drugs that are being developed to respond to tumors harboring aberrant p53 are also described. This book is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with the treatment of this disease.




Genes and Cancer


Book Description

This work serves as an introduction to the applications of molecular biology in the field of oncology. It provides a basic understanding of the genetic events involved in fully developed human cancer, including research into inherited and acquired gene defects initiating new neoplasms and the subsequent genetic alterations involved in tumor progression. Some of the specific topics explored include gene control, molecular therapy and antibodies, drug resistance, growth factors and receptors, and tumor biology. While intended primarily as an advanced text for oncologists, postgraduate molecular geneticists and molecular biologists, the book will certainly be of interest to other researchers who frequently encounter cancer in their practice.




Tumor Models in Cancer Research


Book Description

Beverly A. Teicher and a panel of leading experts comprehensively describe for the first time in many years the state-of-the-art in animal tumor model research. The wide array of models detailed form the basis for the selection of compounds and treatments that go into clinical testing of patients, and include syngeneic models, human tumor xenograft models, orthotopic models, metastatic models, transgenic models, and gene knockout models. Synthesizing many years experience with all the major in vivo models currently available for the study of malignant disease, Tumor Models in Cancer Research provides preclinical and clinical cancer researchers alike with a comprehensive guide to the selection of these models, their effective use, and the optimal interpretation of their results.




The P53 Family


Book Description

This volume offers a comprehensive review of the functions of the p53 family. The contributors examine the normal roles of these transcription factors, their evolution, the regulatory mechanisms that control p53 activity, and the part played by p53 mutations in tumorigenesis.




Medical Epigenetics


Book Description

Medical Epigenetics provides a comprehensive analysis of the importance of epigenetics to health management. The purpose of this book is to fill a current need for a comprehensive volume on the medical aspects of epigenetics with a focus on human systems, epigenetic diseases that affect these systems and modes of treating epigenetic-based disorders and diseases. The intent of this book is to provide a stand-alone comprehensive volume that will cover all human systems relevant to epigenetic maladies and all major aspects of medical epigenetics. The overall goal is to provide the leading book on medical epigenetics that will be useful not only to physicians, nurses, medical students and many others directly involved with health care, but also investigators in life sciences, biotech companies, graduate students and many others who are interested in more applied aspects of epigenetics. Research in the area of translational epigenetics is a cornerstone of this volume. Critical reviews dedicated to the burgeoning role of epigenetics in medical practice Coverage of emerging topics including twin epigenetics as well as epigenetics of gastrointestinal disease, muscle disorders, endocrine disorders, ocular medicine, pediatric diseases, sports medicine, noncoding RNA therapeutics, pain management and regenerative medicine Encompasses a disease-oriented perspective of medical epigenetics as well as diagnostic and prognostic epigenetic approaches to applied medicine




Human Tumor-Derived p53 Mutants: A Growing Family of Oncoproteins


Book Description

TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome. Over the past 3 decades, the regulation of p53 has been extensively studied. However, the regulation of mutant p53 remained largely unexplored. This snapshot focuses on recent discovery of mutant p53 GOF and regulation.




25 Years of p53 Research


Book Description

p53 has emerged as a key tumor suppressor and important target for novel cancer therapy. This book, written by world-leading p53 researchers including many of those who have shaped the field over the past 25 years, provides unique insights into the progress of the field and the prospects for better cancer diagnosis and therapy in the future.




Autophagy and Cancer


Book Description

With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy − what to target and how to target it. ​




The Heterogeneity of Cancer Metabolism


Book Description

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.




Mutant p53 and MDM2 in Cancer


Book Description

This book provides the readers with an overview of research on p53, which has been shown to play a role in numerous crucial biological pathways in normal and cancer cells. Leading scientist in the field, who have all made direct contributions to the understanding of the molecular events underpinning p53 function, have been invited to contribute the various chapters, which discuss the current knowledge of the signaling cascades that are activated by mutations in p53 and overexpression of MDM2, frequently found in human cancer and are major causes of oncogenesis. This book features chapters on the molecular basis of oncogenesis induced by gain of function mutation of p53, signaling pathways induced by MDM2 overexpression, control of mutant or wild-type p53 function by MDM2 and MDMX, p53 mutation in hereditary cancer and structural aspects that activate mutant p53 which can be targeted by drug therapy. This book should be useful for scientists at all levels.