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Targeting the DNA Damage Response for Anti-Cancer Therapy

  • John Pollard
  • Nicola Curtin

Part of the Cancer Drug Discovery and Development book series (CDD&D)

Table of contents

  1. Front Matter
    Pages i-ix
  2. Laura R. Butler, Oren Gilad, Eric J. Brown
    Pages 11-33
  3. Emilio Lecona, Oscar Fernández-Capetillo
    Pages 35-61
  4. Magnus T. Dillon, Kevin J. Harrington
    Pages 99-127
  5. Anika M. Weber, Anderson J. Ryan
    Pages 155-183
  6. Ian Hickson, Kurt G. Pike, Stephen T. Durant
    Pages 185-208
  7. Ian Collins, Michelle D. Garrett
    Pages 241-276
  8. Alvaro Ingles Garces, Udai Banerji
    Pages 277-314
  9. Celine Cano, Suzannah J. Harnor, Elaine Willmore, Stephen R. Wedge
    Pages 339-357
  10. Marie Dutreix, Flavien Devun, Nirmitha Herath, Patricia Noguiez-Hellin
    Pages 359-373
  11. Back Matter
    Pages 401-401

About this book

Introduction

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.

Keywords

DNA repair ATR ATM DNA-PK CHK Synthetic lethality Ionising radiation Chemotherapy resistance

Editors and affiliations

  • John Pollard
    • 1
  • Nicola Curtin
    • 2
  1. 1.Vertex Pharmaceuticals (Europe) LtdAbingdonUnited Kingdom
  2. 2.Northern Institute for Cancer Research, Medical SchoolNewcastle UniversityNewcastle upon TyneUnited Kingdom

Bibliographic information

  • DOI https://doi.org/10.1007/978-3-319-75836-7
  • Copyright Information Springer International Publishing AG, part of Springer Nature 2018
  • Publisher Name Humana Press, Cham
  • eBook Packages Medicine
  • Print ISBN 978-3-319-75834-3
  • Online ISBN 978-3-319-75836-7
  • Series Print ISSN 2196-9906
  • Series Online ISSN 2196-9914
  • Buy this book on publisher's site
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