Chemical genetic approaches to the development of cancer therapeutics

Dysregulation of kinase-based signal transduction networks contributes to multiple aspects of malignancy. Chemical genetic approaches interrogate perturbed signaling in the immediate context of small molecule inhibitor treatment. In recent years, such approaches have identified new kinase targets, clarified the impact of poly-specific inhibition using agents for which at least one primary target is known, and have identified targets for which combinatorial inhibition leads to improved efficacy. Elucidation of the mechanisms through which specific small molecule drug-like agents impact crucial cancer pathways should yield important and clinically translatable insights into the use of similar agents in patients.