DR-184 Combatting therapy resistance in advanced breast cancer

We are investigating drug resistance mechanisms in two different types of breast cancer, 1) invasive lobular carcinoma (ILC) to PI3K/mTOR inhibitors and 2) BRCA-deficient breast cancer to PARP inhibitor. To this end, we used in-vivo mouse models mimicking human ILC and BRCA-deficient breast cancer and obtained drug-resistant tumors through prolonged treatment of mTOR inhibitor and PARP inhibitor. Genomic and proteomic analyses of the treatment-naive/resistant tumors revealed several resistance factors, which were further experimentally validated by in-vitro experiment. To strengthen and validate our findings in clinical relevance, we believe that the HMF WGS, RNA-seq and treatment response data provide valuable resources.

Daniel Zingg Netherlands Cancer Institute the Netherlands