DNA Repair in Cancer Therapy: Molecular Targets and Clinical Applications

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Mark R. Kelley
Academic Press, 2012 - Medical - 316 pages
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Cancer therapeutics include an ever-increasing array of tools at the disposal of clinicians in their treatment of this disease. However, cancer is a tough opponent in this battle, and current treatments, which typically include radiotherapy, chemotherapy and surgery, are not often enough to rid the patient of his or her cancer. Cancer cells can become resistant to the treatments directed at them, and overcoming this drug resistance is an important research focus. Additionally, increasing discussion and research is centering on targeted and individualized therapy. While a number of approaches have undergone intensive and close scrutiny as potential approaches to treat and kill cancer (signaling pathways, multidrug resistance, cell cycle checkpoints, anti-angiogenesis, etc.), other approaches have focused on blocking the ability of a cancer cell to recognize and repair the damaged DNA that primarily results from the front-line cancer treatments; chemotherapy and radiation.

This comprehensive and timely reference 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.



  • Saves academic, medical, and pharmaceutical researchers time in quickly accessing the very latest details on DNA repair and cancer therapy, as opposed to searching through thousands of journal articles
  • Provides a common language for cancer researchers, oncologists, and radiation oncologists to discuss their understanding of new molecular pathways, clinical targets, and anti-cancer drug development
  • Provides content for researchers and research clinicians to understand the importance of the breakthroughs that are contributing to advances in disease-specific research
  

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Contents

From Bench to Clinic
1
A Critical DNA Repair Gene Target for Chemotherapy Resistance and for Stem Cell Protection
17
Inhibition of Small Lesions Results in Big Consequences to Cancer Cells
29
Chapter 4 The Role of PARP in DNA Repair and its Therapeutic Exploitation
55
Chapter 5 Chemotherapeutic Intervention by Inhibiting DNA Polymerases
75
Chapter 6 Targeting the Nucleotide Excision Repair Pathway for Therapeutic Applications
109
Chapter 7 Targeting Homologous Recombination Repair in Cancer
119
Chapter 8 DNA DoubleStrand Break Repair by Nonhomologous End Joining and Its Clinical Relevance
161
Chapter 10 Checkpoint Kinase and Wee1 Inhibitors as Anticancer Therapeutics
211
Implications for Regulation of DNA Repair
235
DNA Repair Alterations Are Promising Predictive Biomarkers in Cancer
257
Chapter 13 The Role of DNA Damage and Repair in Neurotoxicity Caused by Cancer Therapies
283
A Roadmap for Disruptive Approaches to Cancer Therapy
301
Index
311
Color Plates
317
Copyright

Chapter 9 Defective DNA Mismatch Repairdependent cAblp73GADD45α Expression Confers Cancer Chemoresistance
191

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About the author (2012)

Mark R. Kelley, PhD is currently the Betty and Earl Herr Chair in Pediatric Oncology Research, Associate Director for the Herman B Wells Center for Pediatric Research, and the Associate Director of Basic Science Research at the IU Simon Cancer Center. Dr. Kelley's laboratory studies DNA base excision repair in normal and tumor cells, including the study of DNA repair genes in cognitive dysfunction and peripheral neuropathy. He holds 10 patents related to the use of DNA repair targets for cancer therapy and serves on the consulting and scientific boards of several companies. Thus far Dr. Kelley's research resulted in over 160 articles published in peer reviewed journals along with numerous reviews and book chapters.

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