DNA Damage and Repair in Translational Oncology: An Overview

Unknown to early investigators, DNA damage and repair has been a major focus of anticancer therapy from the beginning of clinical oncology. From the early days of using x-irradiation, to the development of nitrogen mustard analogs, to today's more sophisticated approaches, DNA damage and repair...

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Bibliographic Details
Published in:Clinical cancer research 2010-09, Vol.16 (18), p.4511-4516
Main Author: REED, Eddie
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomarkers, Tumor - isolation & purification
DNA Damage - genetics
DNA Damage - physiology
DNA Repair - genetics
DNA Repair - physiology
Evidence-Based Medicine - methods
Humans
Medical Oncology - methods
Medical Oncology - trends
Medical sciences
Neoplasms - genetics
Neoplasms - therapy
Pharmacology. Drug treatments
Signal Transduction - genetics
Translational Medical Research - methods
Translational Medical Research - trends
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Summary:Unknown to early investigators, DNA damage and repair has been a major focus of anticancer therapy from the beginning of clinical oncology. From the early days of using x-irradiation, to the development of nitrogen mustard analogs, to today's more sophisticated approaches, DNA damage and repair has strongly impacted our ability to successfully treat human malignancy. This area of basic, translational, and clinical science is very broad. The traditional focus of DNA damage and repair has been on diseases such as Xeroderma pigmentosum, and attempting to understand the basic molecular mechanisms of DNA repair processes. It is only recently that we have begun to appreciate how we might modulate these processes to improve our ability to advance cancer care. No fewer than 10 separate DNA repair processes are operative in higher organisms, and the total number of separable processes could be substantially higher. Some of our most useful clinical agents depend on causing DNA damage that is repaired by nucleotide excision repair. X-irradiation induces damage that is mostly repaired by base excision repair and double-strand break repair. We are now learning how to modulate select DNA repair pathways to benefit patients with breast cancer and other malignancies.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-10-0528