Therapeutic options for triple negative breast cancers (TNBC) are limited to multiple lines of chemotherapy with no FDA-approved targeted therapies. In the absence of a clear driver oncogene, the most common molecular alterations, including EGF receptor and genes involved in cell cycle, DNA repair and the PI3K pathway, may represent new therapeutic opportunities in TNBC. Indeed clinical benefits from PARP, EGFR and PI3K inhibitors have been reported in some TNBC patient. However, none of these studies have demonstrated durable responses, indicating that inhibition of additional pathways might be necessary to successfully improve the clinical efficacy of targeted therapies in TNBC. To develop novel, combinatorial therapeutic approaches for TNBC we performed a pharmacological screen testing 672 unique drug combinations in multiple TNBC models. The screen identified previously known and efficacious synergies, such as between EGFR and PI3K inhibitors, supporting the validity of our data and analysis. Importantly, we also identified novel promising drug combinations that we are currently exploring.

Citation Format: Carlotta Costa, Anahita Dastur, Rachel Peterson, Damon Leah, Regina Egan, Ryan March, Cyril Benes, Jeffrey Engelman. Uncover novel drug combinations for triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4648.