Protein-Protein Interactions: Emerging Oncotargets in the RAS-ERK Pathway.

Given the implication of aberrant RAS-extracellular signal-regulated kinase (ERK) signaling in the development of a large number of tumor types, this route is under intense scrutiny to identify new anticancer drugs. Most avenues in that direction have been primarily focused on the inhibition of the catalytic activity of the kinases that participate in this pathway. Although promising, the efficacy of these therapies is short lived due to undesired toxicity and/or drug resistance problems. As an alternative path, new efforts are now being devoted to the targeting of protein-protein interactions (PPIs) involved in the flow of RAS-ERK signals. Many of these efforts have shown promising results in preclinical models. In this review, we summarize recent progress made in this area.