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  • Print publication year: 2011
  • Online publication date: February 2014

6 - Implications of homologous recombination defectiveness in ovarian cancer

from SECTION 2 - THE TRANSLATION OF BIOLOGY TO THE CLINIC

Summary

This chapter outlines the DNA repair pathways involved in PARP inhibitor sensitivity, how deficiencies in these pathways are exploited by PARP inhibitors and finally how aberrations of these pathways may be identified and thus used as predictive biomarkers for treatment. Evidence suggests that there can be overlap between the pathways under certain circumstances, for instance in repairing DNA crosslink lesions. There is substantial evidence that tumours associated with germline mutations of the BRCA genes are associated with high initial sensitivity to platinum and overall slightly improved outcome compared with other high-grade serous ovarian cancers. DNA repair pathways would appear to be an attractive target for the development of new therapies. Cancer cells are intrinsically and genetically unstable and therefore susceptible to further DNA damage. Accurate biomarkers would allow identification of people with tumours that are not normally recognised to respond to a particular treatment.