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Comment
. 2021 Aug;11(8):1874-1876.
doi: 10.1158/2159-8290.CD-21-0609.

The gRASs Is Greener: Potential New Therapies in Lung Cancer with Acquired Resistance to KRASG12C Inhibitors

Marika Pinnelli  1   2 , Livio Trusolino  3   2
Affiliations
Comment

The gRASs Is Greener: Potential New Therapies in Lung Cancer with Acquired Resistance to KRASG12C Inhibitors

Marika Pinnelli et al. Cancer Discov. 2021 Aug.

Abstract

Inhibitors of KRASG12C that bind the target in its inactive conformation and lock it in off-mode have shown early signs of clinical activity in patients with KRAS G12C-mutant lung cancer, but responses tend to be short-lived and invariably prelude the development of acquired resistance through largely unexplored mechanisms. A new study describes the emergence of RAS-MAPK heterogeneous subclonal alterations in a patient relapsed on a KRASG12C inactive-state inhibitor and identifies a novel KRASY96D-resistant variant that is druggable by a next-generation compound capable of associating with KRASG12C in its active configuration.See related article by Tanaka et al., p. 1913.

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References

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