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Comment
. 2020 Jan;10(1):20-22.
doi: 10.1158/2159-8290.CD-19-1255.

Can the Help Match the Hype? KRASG12C-Specific Inhibitors and Beyond

Samuel J Klempner  1   2 , Aaron N Hata  3   2
Affiliations
Comment

Can the Help Match the Hype? KRASG12C-Specific Inhibitors and Beyond

Samuel J Klempner et al. Cancer Discov. 2020 Jan.

Abstract

Hallin and colleagues demonstrate the preclinical activity of the KRASG12C-specific inhibitor MRTX849 in a series of in vitro and in vivo studies with supporting pilot clinical efficacy. Variable responsiveness despite effective KRASG12C inhibition highlights both the promise and potential need for combinatorial strategies to optimally target KRASG12C-driven cancers.See related article by Hallin et al., p. 54.

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Comment on

  • The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients.
    Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA, Burkard MR, Fell JB, Fischer JP, Vigers GP, Xue Y, Gatto S, Fernandez-Banet J, Pavlicek A, Velastagui K, Chao RC, Barton J, Pierobon M, Baldelli E, Patricoin EF 3rd, Cassidy DP, Marx MA, Rybkin II, Johnson ML, Ou SI, Lito P, Papadopoulos KP, Jänne PA, Olson P, Christensen JG. Hallin J, et al. Cancer Discov. 2020 Jan;10(1):54-71. doi: 10.1158/2159-8290.CD-19-1167. Epub 2019 Oct 28. Cancer Discov. 2020. PMID: 31658955 Free PMC article.

References

    1. Ryan MB, Corcoran RB. Therapeutic strategies to target RAS-mutant cancers. Nat Rev Clin Oncol. 2018;15:709–20.
    1. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503:548–51.
    1. Govindan R, Fakih M, Price T, Falchook G, Desai J, Kuo J, et al. Phase I study of AMG 510, a novel small molecule targeting KRAS G12C mutant solid tumours. Ann Oncol. 2019;30:mdz244.008.
    1. Janne PA, Papadopoulos K, Ou SH, Rybkin I, Johnson M. A phase I clinical trial evaluating the pharmakokinetics (PK), safety, and clinical activity of MRTX849, a mutant-selective small molecule KRAS G12C inhibitor, in advanced solid tumors.
    1. Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov. 2020.

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