The Ras proteins (coded by the NRAS, KRAS and HRAS genes) were discovered in 1982 and were subsequently found to be some of the most frequently mutated genes in all types of cancer. Mutant Ras proteins are oncogenes (genes that contribute to the initiation and/or progression of tumors) and are therefore obvious targets for the development of new drugs to treat cancer. However, efforts to inhibit Ras proteins with small molecule drugs were thwarted for over 30 years, leading some to declare Ras “undruggable” by this traditional method of drug design.
But the frequency of Ras mutations in cancer and their obvious contribution to tumor development, tumor progression and treatment failure necessitated continued efforts. Here, researchers from M.D. Anderson Cancer Center in Texas (with funding from Amgen) describe clinical success with one such inhibitor – Sotorasib – that targets a specific mutation on KRAS. This is exciting work, but other, more prevalent, mutations on NRAS/KRAS/HRAS are still unable to be targeted clinically. As always, there is much work that remains to be done!
The NEJM Paper
Yahoo News Writeup