Harnessing Synthetic Lethal Interactions for Personalized Medicine

Two genes are said to have synthetic lethal (SL) interactions if the simultaneous mutations in a cell lead to lethality, but each individual mutation does not. Targeting SL partners of mutated cancer genes can kill cancer cells but leave normal cells intact. The applicability of translating this concept into clinics has been demonstrated by three drugs that have been approved by the FDA to target PARP for tumors bearing mutations in BRCA1/2. This article reviews applications of the SL concept to translational cancer medicine over the past five years. Topics are (1) exploiting the SL concept for drug combinations to circumvent tumor resistance, (2) using synthetic lethality to identify prognostic and predictive biomarkers, (3) applying SL interactions to stratify patients for targeted and immunotherapy, and (4) discussions on challenges and future directions.

Automated summary

This article reviews the applications of the synthetic lethal (SL) concept in translational cancer medicine over the past five years. It discusses the use of SL concept in drug combinations to overcome tumor resistance, the identification of prognostic and predictive biomarkers using synthetic lethality, the application of SL interactions in stratifying patients for targeted and immunotherapy, as well as the challenges and future directions in this field.