Development of a Screening Platform for the Identification of Lethality Inducers in Cancer Cells.

CARBAJOSA S.; VILLAFAÑEZ M.F.; SORIA G.; PANSA M.F.; BOCCO J.L.; GARCIA I.A.; GOTTIFREDI V.

Córdoba

Congreso; 52° Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular - SAIB 2016.; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

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 induce selective tumor lethality. The homologous recombination (HR) pathway is a strategic target for synthetic lethality because of its important role in double strand break repair, and because HR loss is a key feature of certain types of breast and ovarian cancer (i.e. BRCA1 and BRCA2 deficient cancers). The aim of this work is to identify new synthetic lethality inducers in HR-deficient cells. To achieve this we developed a high-throughput screening platform based on flow cytometry. This platform is based on the generation of HR-proficient and HR-deficient cell lines of isogenic origin that emulate BRCA1 and BRCA2 deficient cancers, and that can be simultaneously exposed to the tested compounds during the screening. We use fluorescent markers to identify each population, assessing cell survival by the ratio of HR-proficient and HR-deficient populations at the end of the experiment. Here we show the development of the platform and the fine-tuning of the setup using drugs that are known to induce synthetic lethality in a pre-screening phase.