Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer
Technical Report,15 Sep 2014,14 Sep 2019
The Research Institute of Fox Chase Cancer Center Philadelphia United States
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During the course of the grant, we have discovered several novel insights into PARP inhibitor PARPi and cisplatin resistance mechanisms. We showed that the BRCA1-delta11q protein is responsible for promoting PARPi resistance in ovarian cancers with exon 11 located BRCA1 mutations. In another aspect of our studies encompassed within this grant, we discovered that BRCA1185delAG alleles were capable of initiating translation at a start site downstream of the mutation-induced stop codon. We also made a BRCA1 null mouse model and subsequently discovered that 53BP1 knockout only partially restores HR in the absence of BRCA1 hypomorphic proteins. In another recent study, our laboratory showed that BRCA2 mutant alleles are capable of expressing proteins that contribute to PARP inhibitor resistance. These studies were published and OC130212 acknowledged in Wang et al., Cancer Research, 2016 Wang et al., Journal of Clinical Investigation, 2016 Nacson et al., Cell Reports, 2018 Park et al., Molecular Cancer Therapeutics, 2019 and Wang et al., Nature Communications, 2019. In terms of career development, I was promoted to associate professor with tenure in May 2019.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology