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KRASG12C mutation in metastatic colorectal cancer: a new target

    Rebecca Ibrahim

    International Department, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    ,
    Khalil Saleh

    *Author for correspondence: Tel.: +33 142 114 211;

    E-mail Address: khalil_saleh@live.com

    International Department, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    ,
    Claude Chahine

    International Department, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    ,
    Rita Khoury

    International Department, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    ,
    Nadine Khalife

    Department of Head & Neck Oncology, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    &
    Axel Lecesne

    International Department, Gustave Roussy Cancer Campus, Villejuif, 94800, France

    Published Online:https://doi.org/10.2217/fon-2023-0223
    Free first page

    References

    • 1. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 14(2), 89–103 (2019).
    • 2. Tariq K, Ghias K. Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol. Med. 13(1), 120–135 (2016).
    • 3. Won DD, Lee JI, Lee IK, Oh S-T, Jung ES, Lee SH. The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients. BMC Cancer 17(1), 403 (2017).
    • 4. Jancík S, Drábek J, Radzioch D, Hajdúch M. Clinical relevance of KRAS in human cancers. J. Biomed. Biotechnol. 2010, 150960 (2010).
    • 5. Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A. Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol. Res. Pract. 205(12), 858–862 (2009).
    • 6. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503(7477), 548–551 (2013).
    • 7. Jones RP, Sutton PA, Evans JP et al. Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br. J. Cancer 116(7), 923–929 (2017).
    • 8. Reck M, Carbone DP, Garassino M, Barlesi F. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann. Oncol. 32(9), 1101–1110 (2021).
    • 9. Skoulidis F, Li BT, Dy GK et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N. Engl. J. Med. 384(25), 2371–2381 (2021).
    • 10. Fakih MG, Kopetz S, Kuboki Y et al. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 23(1), 115–124 (2022).
    • 11. Weiss J, Yaeger RD, Johnson ML et al. LBA6 KRYSTAL-1: adagrasib (MRTX849) as monotherapy or combined with cetuximab (Cetux) in patients (pts) with colorectal cancer (CRC) harboring a KRASG12C mutation. Ann. Oncol. 32(Suppl. 5), S1294 (2021).
    • 12. Goebel L, Müller MP, Goody RS, Rauh D. KRasG12C inhibitors in clinical trials: a short historical perspective. RSC Med. Chem. 11(7), 760–770 (2020).
    • 13. Singh A, Greninger P, Rhodes D et al. A gene expression signature associated with “K-Ras addiction” reveals regulators of EMT and tumor cell survival. Cancer Cell 15(6), 489–500 (2009).
    • 14. Prenen H, Fakih M, Falchook G et al. SO-39 evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated colorectal cancer: exploratory plasma biomarker analysis of CodeBreaK 100. Ann. Oncol. 33(Suppl. 4), S373 (2022).
    • 15. Amodio V, Yaeger R, Arcella P et al. EGFR blockade reverts resistance to KRASG12C inhibition in colorectal cancer. Cancer Discov. 10(8), 1129–1139 (2020).
    • 16. Ryan MB, Coker O, Sorokin A et al. KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy. Cell Rep. 39(12), 110993 (2022).
    • 17. Kuboki Y, Yaeger R, Fakih M et al. 45MO sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: safety and efficacy for phase Ib full expansion cohort. Ann. Oncol. 33(Suppl. 9), S1445–S1446 (2022).
    • 18. Yaeger R, Weiss J, Pelster MS et al. Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C. New Engl. J. Med. 388(1), 44–54 (2023).
    • 19. Yaeger R, Mezzadra R, Sinopoli J et al. Molecular characterization of acquired resistance to KRASG12C-EGFR inhibition in colorectal cancer. Cancer Discov. 13(1), 41–55 (2023).
    • 20. Canon J, Rex K, Saiki AY et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575(7781), 217–223 (2019).