Olaparib resistance and cisplatin responses in triple negative breast cancer

PARP inhibitor and platinum based drugs such as cisplatin are promising therapies for triple negative breast cancer and exploit the deficiencies in BRCA1 or BRCA2, or homologous recombination repair defects. However, PARP inhibitor resistance is proven to be a major clinical problem. Acquired PARP inhibitor resistance has been linked with co-resistance to platinum-based drugs. To determine how acquired olaparib resistance affects cisplatin response and whether this is influenced by their BRCA1 status, we performed RNAseq transcriptome analysis of isogenic triple negative breast cancer models of olaparib resistance with normal and mutant BRCA1. Overall design: 54 samples - Parental MDA-MB-468 control (3 samples), Parental MDA-MB-468 Olaparib (3 samples), Parental MDA-MB-468 1 uM cisplatin (3 samples), Parental MDA-MB-468 2 uM cisplatin (3 samples), Parental MDA-MB-468 olaparib + 1 uM cisplatin (3 samples), Parental MDA-MB-468 olaparib + 2 uM cisplatin (3 samples), OlaR MDA-MB-468 15 uM olaparib (3 samples), OlaR MDA-MB-468 15 uM + 1 uM cisplatin (3 samples), OlaR MDA-MB-468 15 uM olaparib + 2 uM cisplatin (3 samples), Parental SUM1315 control (3 samples), Parental SUM1315 Olaparib (3 samples), Parental SUM1315 2 uM cisplatin (3 samples), Parental SUM1315 4 uM cisplatin (3 samples), Parental SUM1315 olaparib + 2 uM cisplatin (3 samples), Parental SUM1315 olaparib + 4 uM cisplatin (3 samples), OlaR SUM1315 25 uM olaparib (3 samples), OlaR SUM1315 25 uM + 2 uM cisplatin (3 samples), OlaR SUM1315 25 uM olaparib + 4 uM cisplatin (3 samples)