Editors:
- Brings together experts, who are defining the field of checkpoints, and as such represents a unique collection of insightful contributions that will serve as an important resource for both the research community and the medical oncologists
- Since checkpoint regulation is critical in understanding cancer development and cancer therapy, the interest will be diverse and appeal to both basic and translational investigators alike
Part of the book series: Cancer Drug Discovery and Development (CDD&D)
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Table of contents (17 chapters)
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Targeting Checkpoint Response in Cancer Therapy
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Back Matter
About this book
Much work over the last two decades has firmly established that loss of cell cycle checkpoint regulation, and resultant unabated cellular proliferation, is an inherent characteristic of cancer. This loss may occur through aberration in any single component involved in signal transduction pathways that orchestrate checkpoint regulation, which may manifest through either a failure to activate the checkpoint or a failure to respond to the activated checkpoint. In normal cells, checkpoint pathways are activated when genetic or cellular homeostasis is compromised, and signals are then transduced to re-stabilize homeostasis, and, failing this, to activate the apoptotic machinery to induce a cellular suicidal response. This implies that both survival and cell death pathways are induced following checkpoint activation, and that the final decision is dependant on the net result of integrating the two sets of signals.
It is intriguing that checkpoint pathways are also critical in cancer therapy to provide an apoptotic stimulus when cellular damage induced by the therapeutic agent is detected by the sensor system. Therefore, it is not surprising that failure in pro-survival checkpoint response will render tumor cells hypersensitive to cytotoxics and, conversely, failure in pro-apoptotic checkpoint response will induce genetic instability and/or therapeutic resistance. Understanding the intricacies of checkpoint response is, therefore, central to the design of therapeutic regimen that will enhance antitumor effects. Although early versions of this design entail combination of cytotoxic agents with cell cycle or checkpoint inhibitors, a greater understanding of the concepts could make such combinations clinically more effective. The contributions in this book will consolidate the current state of knowledge on checkpoint responses that may lay the foundation for hypothesis-driven rational approaches in advancing the management of cancer.
The immediate attraction of the book to the scientific community is that it represents a timely opportunity to build upon existing concepts of checkpoints to expand our understanding of the inner workings of the critical checkpoint machinery. The present understanding has provided ample appreciation that response to checkpoint activation is manifested through coordinated inhibition of cyclin-dependent kinase (CDK) complexes in G1, S and/or the G2 phase in order to arrest the cell cycle. Kinase inhibition can occur through several mechanisms, including inhibitory phosphorylation of CDK, destruction of the cognate cyclins, and recruitment of CDK inhibitors from the INK and WAF1/CIP1 families. However, the wealth of information from recent discoveries needs to be examined critically to consolidate our conceptual knowledge of checkpoints. At the same time, there is acute awareness in the diversity of checkpoint response between cytotoxic agents, and this serves as a reminder of the magnitude of complexity that is inherent in checkpoint regulation. This volume is intended to bring the cancer research community closer toward an improved understanding of this regulation, how checkpoint abnormalities can impact negatively on cancer therapy, and emerging strategies to target checkpoint response as a therapeutic end-point.
Reviews
Editors and Affiliations
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M.D. Anderson Cancer Center, University of Texas, Houston, U.S.A.
Zahid H. Siddik
Bibliographic Information
Book Title: Checkpoint Controls and Targets in Cancer Therapy
Editors: Zahid H. Siddik
Series Title: Cancer Drug Discovery and Development
DOI: https://doi.org/10.1007/978-1-60761-178-3
Publisher: Humana Totowa, NJ
eBook Packages: Medicine, Medicine (R0)
Copyright Information: Humana Press 2009
Hardcover ISBN: 978-1-60761-177-6Published: 07 September 2009
Softcover ISBN: 978-1-61779-635-7Published: 07 March 2012
eBook ISBN: 978-1-60761-178-3Published: 12 March 2010
Series ISSN: 2196-9906
Series E-ISSN: 2196-9914
Edition Number: 1
Number of Pages: XIV, 274
Number of Illustrations: 30 b/w illustrations, 13 illustrations in colour
Topics: Cancer Research, Oncology, Pharmacology/Toxicology
Industry Sectors: Biotechnology, Consumer Packaged Goods, Health & Hospitals, Pharma