Vivek Subbiah, MD, on Data from AACR on Resistance Mechanisms to KRAS Inhibitors


CancerNetwork® spoke with Vivek Subbiah, MD, during the virtual American Association for Cancer Research Annual Meeting 2021 to discuss the most important data to come out of the meeting regarding therapy for tumors harboring KRAS mutations.

CancerNetwork® spoke with Vivek Subbiah, MD, about data regarding mechanisms of resistance to investigational KRAS G12C inhibitors that was presented at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.1 The abstract he spotlighted explored the use of adagrasib and sotorasib in patients with non–small cell lung cancer or colorectal cancer and mutations in KRAS G12C.


AACR was phenomenal in terms of presenting data on resistance mechanisms, specifically to this gene called KRAS. As we all know, KRAS has been called the “undruggable gene.” Last year, there was a publication from one of our MD Anderson [Cancer Center] colleagues in the New England Journal of Medicine [which had] the first data showing that KRAS G12C could be inhibited by a kinase inhibitor.2 Since then on, the field has quickly moved on to analyze the response and more importantly, the resistance mechanisms to this KRAS G12C, specifically with 2 drugs in clinical trials. I think this was one of the major presentations at AACR.


1. Awad M, Liu S, Arbour K, et al. Mechanisms of acquired resistance to KRAS G12C inhibition in cancer. Presented at: the American Association for Cancer Research Annual Meeting 2021. April 9-14, 2021. Virtual. Abstract LB002.

2. Hong DS, Fakih MG, Strickler JH, et al. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239

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