Development of screening platforms for the identification of synthetic lethality inducers in homologous-recombination-deficient cancer cells

VILLAFAÑEZ, F; PANSA, MF; CARBAJOSA, S; GARCIA, AI; BOCCO, JL; SORIA, G

Montevideo

Congreso; X Congreso ALAMCTA II Congreso Sociedad Uruguaya de Radioprotección I Jornada de Salud y Toxicología Ambiental; 2016

Asociación Latinoamericana Mutagénesis, Carcinogénesis y Teratogénesis Ambiental

One of the current challenges in the fight against cancer is the identification of compounds with selective tumor cytotoxicity. A precision strategy of this kind that lead to promising results in recent years is the induction of synthetic lethality, which takes advantage of tumor mutations to trigger selective tumor cell death. The homologous recombination (HR) pathway is a strategic target for synthetic lethality due to its important role in double strand break repair, and also because HR loss is a distinctive feature of certain types of breast and ovarian cancer (i.e. BRCA1 and BRCA2 deficient cancers). The aim of this work is to identify novel targets to induce synthetic lethality in HR-deficient cells. To this end we have developed cell-based phenotypic screenings with different throughput capacities, following both top-down and bottom-up approaches. In my presentation I will present the strategy and setup of a top-down high-throughput platform, as well as the results of a pilot screening using an open source library of kinase inhibitors from GlaxoSmithKline.