Research Projects

Cancer cells have an unabated proliferative capacity due to mutations in genes involved in cell cycle regulation and DNA repair. Hyperactivation of DNA repair genes can lead to survival advantages, tumorigenesis, and chemoresistance. Impairment of repair pathways increases the cells' susceptibility to genotoxic stresses. Clastogenic drugs like doxorubicin induce double-strand breaks in DNA, but cell repair mechanisms can lead to resistance. To avoid this, a hybrid prodrug, MirDox, is designed to activate mirin and doxorubicin specifically in cancer cells. The cytotoxicity of MirDox will be evaluated in chemo-sensitive and resistant cancer cell lines using cell viability and proliferation assays, cell cycle analysis, and annexin V staining. The study will also test if MirDox inhibits cell proliferation and affects DNA damage response and repair in an MRE11-dependent manner. The effect of MirDox will be studied on in vitro cancer spheroids isolated from post-surgical oesophageal cancer tissues. This study opens new perspectives for designing anti-cancer therapies to overcome resistance and expand the horizon for using DNA repair inhibitors in targeted therapy.