[Exploiting synthetic lethality for cancer precision medicine]
Synthetic lethality is a genetic interaction where a single gene deficiency is tolerable for cell viability while the combination of deficiencies in two genes leads to cell death. The concept of the synthetic lethality has been widely exploited in cancer research field because a large portion of cancer has loss-of-function mutations in tumor suppressor genes. Synthetic lethality utilizes the mutations in tumor suppressor genes as a mark for selectivity of anticancer drugs. Pharmacological or genetic perturbation of a synthetic lethality partner of a tumor suppressor will cause selective lethality of the cancer cells that carry the tumor suppressor mutation. As it provides a strong cancer cell selectivity, synthetic lethality is one of core approaches for cancer precision medicine.
My lab is studying major tumor suppressor genes, including p53, PTEN, RB1, BRCA1, ARID1A, and SMAD4, and is expanding to newly identified tumor suppressors. We have established isogenic cell pairs for the tumor suppressor genes and actively working on identifying synthetic lethality partners using chemical and genetic screenings.