MSE-4025-0 Dissertation

Abstract

Synthetic lethality showed promising results in cancer therapy. Fanconi anaemia (FA) is a hereditary disease with high cancer susceptibility. Many complications were reported due to chemotherapeutics use by FA patients, so more targeted treatments are needed. In this study, we investigated if the inhibition of both MRE11 and DNA2 nuclease activities by using Mirin and C5 respectively, will improve the repair sensitivity of FANCD2 mutated cells. Western blot confirmed the expression of FANCD2 protein only in PD20 RV2 (control) and its absence in PD20 cells (FANCD2 -/-). However, although Mitomycin C (MMC) sensitivity assay and drug dose-response assays (with Mirin, C5, and their synergy) showed a decrease in both cell lines' survival with increasing the doses of the drugs, PD20 RV: D2 cells expressed slightly more sensitivity towards MMC compared to PD20 cells. These unexpected results may be in part due to cellular adaptations.