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Targeted therapy

Precision oncology for KRASG12C-mutant colorectal cancer

Nature Reviews Clinical Oncology volume 20, pages 355–356 (2023)Cite this article

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Allele-specific inhibitors of KRASG12C are approved in non-small-cell lung cancer. Herein, we discuss recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRASG12C-mutant metastatic colorectal cancer. The combination had promising efficacy and, if confirmed in later-phase trials, concomitant inhibition of EGFR and KRASG12C will present a new paradigm in precision oncology.

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Acknowledgements

The authors thank G. Mauri, G. Patelli, P. P. Vitiello and A. Cavaliere at the University of Torino and University of Milano, for critically reading this manuscript. Work in the authors’ laboratories has been supported by funding from AIRC under 5 per Mille 2018 - ID. 21091 programme (with A.B. as Principal Investigator and F.D.N. as Group Leader); AIRC under IG 2018 - ID. 21923 project (to A.B.) and ID. 21091 project (to F.D.N.); International Accelerator Award, ACRCelerate, jointly funded by Cancer Research UK (A26825 and A28223), FC AECC (GEACC18004TAB) and AIRC (22795) (to A.B.); and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (TARGET grant agreement No 101020342 to A.B.).

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Authors and Affiliations

  1. Department of Oncology, University of Torino, Candiolo, Turin, Italy

    Federica Di Nicolantonio & Alberto Bardelli

  2. Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy

    Federica Di Nicolantonio

  3. IFOM-ETS, The AIRC Institute of Molecular Oncology, Milan, Italy

    Alberto Bardelli

Authors
  1. Federica Di Nicolantonio
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  2. Alberto Bardelli
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Correspondence to Federica Di Nicolantonio or Alberto Bardelli.

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Competing interests

F.D.N. has received speaker’s fees from Pierre Fabre for participating in an advisory board meeting relating to encorafenib. A.B. reports receiving commercial research grants from AstraZeneca, Boehringer Ingelheim and Neophore; is an advisory board member/unpaid consultant for Inivata and Neophore; has ownership interest in Neophore; and is an advisory board member/consultant for Guardant Health, Illumina, Inivata and Roche/Genentech.

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cBioPortal: https://www.cbioportal.org/

ClinicalTrials.gov: https://clinicaltrials.gov/

Global Cancer Observatory: https://gco.iarc.fr/today/home

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Di Nicolantonio, F., Bardelli, A. Precision oncology for KRASG12C-mutant colorectal cancer. Nat Rev Clin Oncol 20, 355–356 (2023). https://doi.org/10.1038/s41571-023-00748-z

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