A Road Map to Personalizing Targeted Cancer Therapies Using Synthetic Lethality

Abstract

Targeted therapies rely on the genetic and epigenetic status of the tumor cells and are seen as the most promising approach to treat cancer today. However, current targeted therapies focus on directly inhibiting those molecules that are altered in tumor cells. Unfortunately, targeting these molecules, even with specific inhibitors, is challenging as tumor cells rewire their genetic circuitry to eliminate genetic dependency on these targets. Here, we describe how synthetic lethality approaches can be used to identify genetic dependencies and develop personalized targeted therapies. We also discuss strategies to specifically target these genetic dependencies, using small molecule and biologic drugs.

Keywords: shRNA vs CRISPR; synthetic lethality; targeting intracellular molecules.