[PDF] Cancer Drugs Targeting Dna Replication Molecular Strategies To Enhance Specificity And Efficacy eBook
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The DNA molecule stands at the center of cancer origin and treatment. Cancer cells are addicted to DNA mutations and DNA replication, therapeutic non-responders are often based on the rate of mutations and ability to replicate DNA. Conversely, DNA, being the most vulnerable spot of a tumor, is also the main target for chemotherapies. The in-depth understanding of cellular processes upon errors in the DNA genetic code is therefore crucial for designing new chemotherapeutic drugs and new combinations of drugs; specifically, it is the main endeavor to induce and exacerbate DNA damage in cancer...
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.
Poly (ADP-ribose) polymerase (PARP), also termed poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme with a wide range of functions, including regulation of DNA repair, cell differentiation, and gene expression. More than a decade after the identification of PARP-like enzymatic activities in mammalian cells, a novel role was proposed for this e
Provides a comprehensive overview of all major areas of cancer research and oncology. Bridging the gap between the molecular biology of cancer and clinical diagnosis and treatment, this online reference work provides a resource for medical and life sciences students, as well as all scientists, clinicians and researchers working in the cancer field and related biomedical areas.
Author : Kelly K. Hunt Publisher : Springer Science & Business Media Page : 469 pages File Size : 28,47 MB Release : 2007-10-26 Category : Medical ISBN : 159745222X
The three sections of this volume present currently available cancer gene therapy techniques. Part I describes the various aspects of gene delivery. In Part II, the contributors discuss strategies and targets for the treatment of cancer. Finally, in Part III, experts discuss the difficulties inherent in bringing gene therapy treatment for cancer to the clinic. This book will prove valuable as the volume of preclinical and clinical data continues to increase.
Author : John A. Hickman Publisher : Springer Science & Business Media Page : 347 pages File Size : 41,32 MB Release : 1999-04-08 Category : Medical ISBN : 1592597203
The past few years have witnessed an astonishing international effort that established the role of some 20 new molecules in apoptosis and added activation or suppression of apoptosis to the accepted biological functions of a great many others already familiar in cancer biology. Some of these molecules are receptors, transducing cytokine-mediated signals; others appear to intensify or diminish the risk that a compro mised cell will fire its apoptosis effector mechanism. All are of interest as potential targets for tumor therapy, and some may prove to be control points influenced in the pathogenesis of cancer and other diseases as diverse as viral infection, neurodegenerative disorders, and stroke. Sometimes, in the midst of these developments, a kind of euphoria ap pears to have gripped the research community, with the expectation that apoptosis will afford explanations to many unsolved questions in cellu lar regulation. This book, in a series of thoughtful and provocative ar ticles--some from established leaders in the field, and others from younger scientists--seeks to redress the balance.
DNA Repair and Cancer Therapy: Molecular Targets and Clinical Applications, Second Edition provides a comprehensive and timely reference that focuses on the translational and clinical use of DNA repair as a target area for the development of diagnostic biomarkers and the enhancement of cancer treatment. Experts on DNA repair proteins from all areas of cancer biology research take readers from bench research to new therapeutic approaches. This book provides a detailed discussion of combination therapies, in other words, how the inhibition of repair pathways can be coupled with chemotherapy, radiation, or DNA damaging drugs. Newer areas in this edition include the role of DNA repair in chemotherapy induced peripheral neuropathy, radiation DNA damage, Fanconi anemia cross-link repair, translesion DNA polymerases, BRCA1-BRCA2 pathway for HR and synthetic lethality, and mechanisms of resistance to clinical PARP inhibitors. Provides a comprehensive overview of the basic and translational research in DNA repair as a cancer therapeutic target Includes timely updates from the earlier edition, including Fanconi Anemia cross-link repair, translesion DNA polymerases, chemotherapy induced peripheral neuropathy, and many other new areas within DNA repair and cancer therapy Saves academic, medical, and pharma researchers time by allowing them to quickly access the very latest details on DNA repair and cancer therapy Assists researchers and research clinicians in understanding the importance of the breakthroughs that are contributing to advances in disease-specific research
The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.