Exploiting Dna Damage Response In The Era Of Precision Oncology

Topic Editor Christian Reinhardt has received funding from companies Gilead, and lecture fees from Abbvie, Merck, and AstraZeneca. All other topic editors declare no competing interests with regards to the Research Topic subject.

This book discusses the latest developments in Poly (ADP-ribose) polymerase (PARP) inhibitor drug development. It focuses on the translational and clinical development of the latest drugs, as well as the evidence for regulatory approval of PARP inhibitors in multiple different molecular subtypes and tumor indications. The most-up-to-date information on basic scientific research on DNA repair pathways and the DNA Damage Response (DDR) is also covered. Every chapter contains insight into the preclinical, translational along with clinical aspects of a specific DDR inhibitor with key and expert opinion points reinforcing the most important concepts detailed to enable the reader to develop a deep understanding of the topic. Targeting the DNA Damage Response for Cancer Therapy comprehensively reviews the application of PARP and other DDR inhibitors across oncology disciplines. Therefore, it is a valuable resource for all medical professionals and researchers who use or who are researching the use of these inhibitors on a day-to-day basis.

Over the past decade a complex role for DNA damage response (DDR) in tumorigenesis has emerged. A proficient DDR has been shown to be a primary cause for cellular resistance to the very many DNA damaging drugs, and IR, that are widely used as standard-of-care across multiple cancer types. It has also been shown that defects in this network, predominantly within the ATM mediated signaling pathway, are commonly observed in cancers and may be a primary event during tumorigenesis. Such defects may promote a genomically unstable environment, facilitating the persistence of mutations, any of which may provide a growth or survival advantage to the developing tumor. In addition, these somatic defects provide opportunities to exploit a reliance on remaining repair pathways for survival, a process which has been termed synthetic lethality. As a result of all these observations there has been a great interest in targeting the DDR to provide anti-cancer agents that may have benefit as monotherapy in cancers with high background DNA damage levels or as a means to increase the efficacy of DNA damaging drugs and IR. In this book we will review a series of important topics that are of great interest to a broad range of academic, industrial and clinical researchers, including the basic science of the DDR, its role in tumorigenesis and in dictating response to DNA damaging drugs and IR. Additionally, we will focus on the several proteins that have been targeted in attempts to provide drug candidates, each of which appear to have quite distinct profiles and could represent very different opportunities to provide patient benefit.

Chromatin and DNA Repair in Cancer, Volume 364 in the International Review of Cell and Molecular Biology series reviews and details current advances in cell and molecular biology. Chapters in this new release cover Genomic Instability and metabolism in cancer, Histones variants and Histones modifications in cancer and Aging, DNA Double-stranded breaks Repair in Cancer, Reactive oxygen species and DNA damage response in cancer, Transcription-Associated DNA Breaks and Cancer: A Matter of DNA Topology, Mechanisms of Base Excision Repair: Its Significance to Human Health, and more. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. The articles published in IRCMB have a high impact and an average cited half-life of 9 years. This great resource ranks high amongst scientific journals dealing with cell biology. Publishes only invited review articles on selected topics Authored by established and active cell and molecular biologists, drawn from international sources Offers a wide range of perspectives on specific subjects

Genomic sequencing technologies have augmented the classification of cancer beyond tissue of origin and towards a molecular taxonomy of cancer. This has created opportunities to guide treatment decisions for individual patients with cancer based on their cancer’s unique molecular characteristics, also known as precision cancer medicine. The purpose of this text will be to describe the contribution and need for multiple disciplines working together to deliver precision cancer medicine. This entails a multi-disciplinary approach across fields including molecular pathology, computational biology, clinical oncology, cancer biology, drug development, genetics, immunology, and bioethics. Thus, we have outlined a current text on each of these fields as they work together to overcome various challenges and create opportunities to deliver precision cancer medicine. As trainees and junior faculty enter their respective fields, this text will provide a framework for understanding the role and responsibility for each specialist to contribute to this team science approach.

Progress and Challenges in Precision Medicine presents an insightful overview to the myriad factors of personalized and precision medicine. The availability of the human genome, large amounts of data on individual genetic variations, environmental interactions, influence of lifestyle, and cutting-edge tools and technologies for big-data analysis have led to the age of personalized and precision medicine. Bringing together a global range of experts on precision medicine, this book collects previously scattered information into one concise volume which covers the most important developments so far in precision medicine and also suggests the most likely avenues for future development. The book includes clinical information, informatics, public policy implications, and information on case studies. It is a useful reference and background work for students, researchers, and clinicians working in the biomedical and medical fields, as well as policymakers in the health sciences. Provides an overview of the growing field of precision medicine Contains chapters from geographically diverse experts in their field Explores important aspects of precision medicine, including applications, ethics, and development

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the “DNA damage response”. This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

This book provides up-to-date coverage of selected topics in nucleic acid oxidation. The topics have been selected to cover everything from basic chemical mechanisms, repair of damage and the biological and pathological meaning of DNA oxidation. The chapters are authored by leading, research active, international experts in the respective topics.