Mutator Phenotypes that Better Predict PARP Inhibitor Response in Ovarian Carcinomas
Technical Report,01 Aug 2017,31 Jul 2018
University of Washington Seattle United States
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Many ovarian cancers have specific defects in DNA repair that make them sensitive to a new class of drugs called PARP inhibitors. PARP inhibitors are particularly effective against cancers that have alterations in the BRCA1 or BRCA2 genes. BRCA1 and BRCA2 function in DNA repair, and cancers associated with BRCA1 or BRCA2 mutations are deficient in homologous recombination directed DNA repair. When homologous recombination does not work right, cancer cells rely on other types of DNA repair that result in more errors in replicating DNA, leading to characteristic patterns of DNA alterations. Whole genome sequencing can detect patterns of alterations in the DNA that are characteristic of homologous recombination deficiency. We will perform whole genome sequencing on cancers from 120 women who participated in ARIEL2, a PARP inhibitor clinical trial for recurrent ovarian cancer. We will use the information that we acquire to develop a new clinical test based on patterns of DNA alterations to better predict which women with ovarian cancer should be treated with a PARP inhibitor. In this manner, we can identify women with ovarian cancer who do not have BRCA1 or BRCA2 mutations, but who also have a good chance of responding to PARP inhibitors.
- Medicine and Medical Research