Therapeutic targeting of RAS: New hope for drugging the “undruggable”

Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Imran Khan, J. Matthew Rhett, John P. O'BryanAbstractRAS is the most frequently mutated oncogene in cancer and a critical driver of oncogenesis. Therapeutic targeting of RAS has been a goal of cancer research for>30 years due to its essential role in tumor formation and maintenance. Yet the quest to inhibit this challenging foe has been elusive. Although once considered “undruggable”, the struggle to directly inhibit RAS has seen recent success with the development of pharmacological agents that specifically target the KRAS(G12C) mutant protein, which include the first direct RAS inhibitor to gain entry to clinical trials. However, the limited applicability of these inhibitors to G12C-mutant tumors demands further efforts to identify more broadly efficacious RAS inhibitors. Understanding allosteric influences on RAS may open new avenues to inhibit RAS. Here, we provide a brief overview of RAS biology and biochemistry, discuss the allosteric regulation of RAS, and summarize the various approaches to develop RAS inhibitors.

Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - October 31, 2019 Category: Molecular Biology Source Type: research