Abstract A03: Several rational combination kinase inhibitor treatments identified by synthetic lethality screens are efficacious in intracranial triple negative breast cancer models

Conclusions: Synthetic lethality screens identified multiple rational combination therapies based on PI3K and/or MEK inhibition in TNBC cells, particularly PI3K+MEK, MEK+PDGFR, and PI3K+AURKA. Combined use of brain-penetrant, clinically available inhibitors against these targets showed promising efficacy in intracranial TNBC mouse models. Rational combinations of brain-penetrant kinase inhibitors are promising strategies for a patient population with few options. In vivo studies assessing the efficacy of other identified combinations, as well as more extensive characterization of potential resistance mechanisms, in intracranial TNBC mouse models are warranted to provide the translational foundation for future clinical studies.Citation Format: Amanda E.D. Van Swearingen, Maria J. Sambade, Marni B. Siegel, Shivani Sud, Samantha M. Bevill, Brian T. Golitz, Ryan E. Bash, Charlene M. Santos, David B. Darr, Joel S. Parker, C. Ryan Miller, Gary L. Johnson, Carey K. Anders. Several rational combination kinase inhibitor treatments identified by synthetic lethality screens are efficacious in intracranial triple negative breast cancer models [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr A03.

Source: Molecular Cancer Therapeutics - October 2, 2017 Category: Cancer & Oncology Authors: Swearingen, A. E. D. V., Sambade, M. J., Siegel, M. B., Sud, S., Bevill, S. M., Golitz, B. T., Bash, R. E., Santos, C. M., Darr, D. B., Parker, J. S., Miller, C. R., Johnson, G. L., Anders, C. K. Tags: Model Organisms to Identify Synthetic Lethal Interactions: Poster Presentations - Proffered Abstracts Source Type: research