Progress of KRAS G12C inhibitors in the treatment of refractory colorectal cancer and strategies for drug resistance response

Severi C, Van Cutsem E (2022) KRAS G12C inhibition with sotorasib in metastatic colorectal cancer. Ann Palliat Med 11:2792–2795. https://doi.org/10.21037/apm-22-532

Article  PubMed  Google Scholar 

Henry JT, Coker O, Chowdhury S et al (2021) Comprehensive clinical and molecular characterization of KRAS (G12C)-mutant colorectal cancer. JCO Precis Oncol 5:613–621. https://doi.org/10.1200/po.20.00256

Article  Google Scholar 

Salem ME, El-Refai SM, Sha W et al (2022) Landscape of KRAS(G12C), Associated genomic alterations, and interrelation with immuno-oncology biomarkers in KRAS-mutated cancers. JCO Precis Oncol 6:e2100245. https://doi.org/10.1200/po.21.00245

Article  PubMed  PubMed Central  Google Scholar 

Ottaiano A, Normanno N, Facchini S et al (2020) Study of Ras mutations’ prognostic value in metastatic colorectal cancer: STORIA analysis. Cancers 12:1919. https://doi.org/10.3390/cancers12071919

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ottaiano A, Sabbatino F, Perri F et al (2023) KRAS p.G12C mutation in metastatic colorectal cancer: prognostic implications and advancements in targeted therapies. Cancers 15:3579. https://doi.org/10.3390/cancers15143579

Article  PubMed  PubMed Central  CAS  Google Scholar 

John J, Sohmen R, Feuerstein J et al (1990) Kinetics of interaction of nucleotides with nucleotide-free H-ras p21. Biochemistry 29:6058–6065. https://doi.org/10.1021/bi00477a025

Article  PubMed  CAS  Google Scholar 

Pamonsinlapatham P, Hadj-Slimane R, Lepelletier Y et al (2009) p120-Ras GTPase activating protein (RasGAP): a multi-interacting protein in downstream signaling. Biochimie 91:320–328. https://doi.org/10.1016/j.biochi.2008.10.010

Article  PubMed  CAS  Google Scholar 

Ostrem JM, Peters U, Sos ML et al (2013) K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503:548–551. https://doi.org/10.1038/nature12796

Article  PubMed  PubMed Central  CAS  Google Scholar 

Blair HA (2021) Sotorasib: first approval. Drugs 81:1573–1579. https://doi.org/10.1007/s40265-021-01574-2

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dhillon S (2023) Adagrasib: first approval. Drugs 83:275–285. https://doi.org/10.1007/s40265-023-01839-y

Article  PubMed  CAS  Google Scholar 

Brazel D, Nagasaka M (2024) Divarasib in the evolving landscape of KRAS G12C inhibitors for NSCLC. Target Oncol 19:297–301. https://doi.org/10.1007/s11523-024-01055-y

Article  PubMed  PubMed Central  Google Scholar 

Lanman BA, Allen JR, Allen JG et al (2020) Discovery of a covalent inhibitor of KRAS(G12C) (AMG 510) for the treatment of solid tumors. J Med Chem 63:52–65. https://doi.org/10.1021/acs.jmedchem.9b01180

Article  PubMed  CAS  Google Scholar 

Krishnan T, Roberts-Thomson R, Broadbridge V et al (2022) Targeting mutated KRAS genes to treat solid tumours. Mol Diagn Ther 26:39–49. https://doi.org/10.1007/s40291-021-00564-0

Article  PubMed  CAS  Google Scholar 

Di Federico A, Ricciotti I, Favorito V et al (2023) Resistance to KRAS G12C inhibition in non-small cell lung cancer. Curr Oncol Rep 25:1017–1029. https://doi.org/10.1007/s11912-023-01436-y

Article  PubMed  CAS  Google Scholar 

Ji J, Wang C, Fakih M (2022) Targeting KRAS (G12C)-mutated advanced colorectal cancer: research and clinical developments. Onco Targets Ther 15:747–756. https://doi.org/10.2147/ott.S340392

Article  PubMed  PubMed Central  Google Scholar 

Ye W, Lu X, Qiao Y et al (2024) Activity and resistance to KRAS(G12C) inhibitors in non-small cell lung cancer and colorectal cancer. Biochim Biophys Acta 1879:189108. https://doi.org/10.1016/j.bbcan.2024.189108

Article  CAS  Google Scholar 

Manabe T, Bivona TG (2022) Remodeling of the tumor/tumor microenvironment ecosystem during KRAS G12C inhibitor clinical resistance in lung cancer. J Clin Investig 132. https://doi.org/10.1172/jci156891

Hondo N, Kitazawa M, Koyama M et al (2023) MEK inhibitor and anti-EGFR antibody overcome sotorasib resistance signals and enhance its antitumor effect in colorectal cancer cells. Cancer Lett 567:216264. https://doi.org/10.1016/j.canlet.2023.216264

Article  PubMed  CAS  Google Scholar 

Zhao Y, Murciano-Goroff YR, Xue JY et al (2021) Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature 599:679–683. https://doi.org/10.1038/s41586-021-04065-2

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ning W, Marti TM, Dorn P et al (2022) Non-genetic adaptive resistance to KRAS(G12C) inhibition: EMT is not the only culprit. Front Oncol 12:1004669. https://doi.org/10.3389/fonc.2022.1004669

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shao DD, Xue W, Krall EB et al (2014) KRAS and YAP1 converge to regulate EMT and tumor survival. Cell 158:171–184. https://doi.org/10.1016/j.cell.2014.06.004

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rougier P, Van Cutsem E, Bajetta E et al (1998) Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet (London, England) 352:1407–1412. https://doi.org/10.1016/s0140-6736(98)03085-2

Article  PubMed  CAS  Google Scholar 

Van Cutsem E, Hoff PM, Harper P et al (2004) Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 90:1190–1197. https://doi.org/10.1038/sj.bjc.6601676

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ciardiello D, Maiorano BA, Martinelli E (2023) Targeting KRAS(G12C) in colorectal cancer: the beginning of a new era. ESMO Open 8:100745. https://doi.org/10.1016/j.esmoop.2022.100745

Article  PubMed  CAS  Google Scholar 

Hong DS, Fakih MG, Strickler JH et al (2020) KRAS(G12C) Inhibition with sotorasib in advanced solid tumors. N Engl J Med 383:1207–1217. https://doi.org/10.1056/NEJMoa1917239

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kinahan H (2022) A rare event of liver dysfunction on sotorasib and management strategy. J Adv Pract Oncol 13:812–815. https://doi.org/10.6004/jadpro.2022.13.8.7

Article  PubMed  PubMed Central  Google Scholar 

Fakih MG, Kopetz S, Kuboki Y et al (2022) Sotorasib for previously treated colorectal cancers with KRAS(G12C) mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol 23:115–124. https://doi.org/10.1016/s1470-2045(21)00605-7

Article  PubMed  CAS  Google Scholar 

Pelster MS, Yaeger R, Klempner SJ et al (2023) Adagrasib with or without cetuximab in patients with KRASG12C-mutated colorectal cancer (CRC): analysis of tumor biomarkers and genomic alterations. Ann Oncol 34:S410–S410. https://doi.org/10.1016/j.annonc.2023.09.1740

Article  Google Scholar 

Riely GJ, Ou SHI, Rybkin I et al (2021) KRYSTAL-1: activity and preliminary pharmacodynamic (PD) analysis of adagrasib (MRTX849) in patients (Pts) with advanced non-small cell lung cancer (NSCLC) harboring KRASG12C mutation. J Thorac Oncol 16:S751–S752

Article 

Comments (0)

No login
gif