Approximately 25% to 30% of human metastatic breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). However, most tumors ultimately develop therapeutic resistance to current HER2 targeted therapy, leading to disease progression. Neratinib (HKI-272), a tyrosine kinase inhibitor, is an irreversible inhibitor of HER1, HER2, and HER4, has been reported as highly active against HER-2 + human breast cancer cells. Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor defects DNA repair, induce serious cytotoxicity in cancer cells. We hypothesize that the addition of Olaparib to Neratinib will increase cell death in HER2 overexpressed breast cancer cells. In this study, we performed cell proliferation assay to measure the cell growth with the combination treatment in selected HER positive breast cancer MDA-MB 361 cells. The results confirmed that combined PARP and HER2/EGFR inhibitors have a synergistic effect on decreasing cell growth. This can be an innovative treatment strategy to potentially improve outcomes in HER2+, especially in BRCA mutated patients.

Combining PARP inhibitor olaparib and HER2/EGFR inhibitor in HER2 positive breast cancer cells

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.