{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:54:20Z","timestamp":1790963660297,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to-cysteine mutation at codon 12 (KRAS G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations. In recent years, several KRAS G12C inhibitors have demonstrated clinical activity, although all patients eventually progressed. The identification of negative feedback through the EGFR receptor has led to the development of KRAS inhibitors plus an anti-EGFR combination, thus boosting antitumor activity. Currently, several KRAS G12C inhibitors are under development, and results from phase I and phase II clinical trials are promising. Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine\/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation. Nonetheless, most of these patients will eventually relapse. In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.<\/jats:p>","DOI":"10.3390\/ijms25063304","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T09:32:30Z","timestamp":1710495150000},"page":"3304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-5415","authenticated-orcid":false,"given":"Javier","family":"Ros","sequence":"first","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Vaghi","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"},{"name":"Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-9641","authenticated-orcid":false,"given":"Iosune","family":"Baraibar","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Saoudi Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rodr\u00edguez-Castells","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Alcaraz","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Salva","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-8139","authenticated-orcid":false,"given":"Josep","family":"Tabernero","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Elez","sequence":"additional","affiliation":[{"name":"Medical Oncology, Vall d\u2019Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain"},{"name":"Medical Oncology, Vall d\u2019Hebron Universite Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive Molecular Characterization of Human Colon and Rectal Cancer","volume":"487","author":"Muzny","year":"2012","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic Colorectal Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-up \u2606","volume":"34","author":"Cervantes","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1056\/NEJMoa1414325","article-title":"Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer","volume":"372","author":"Mayer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1056\/NEJMoa2214963","article-title":"Trifluridine\u2013Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer","volume":"388","author":"Prager","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0140-6736(12)61900-X","article-title":"Regorafenib Monotherapy for Previously Treated Metastatic Colorectal Cancer (CORRECT): An International, Multicentre, Randomised, Placebo-Controlled, Phase 3 Trial","volume":"381","author":"Grothey","year":"2013","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1200\/PO.20.00256","article-title":"Comprehensive Clinical and Molecular Characterization of KRAS G12C -Mutant Colorectal Cancer","volume":"6","author":"Henry","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/bjc.2017.37","article-title":"Specific Mutations in KRAS Codon 12 Are Associated with Worse Overall Survival in Patients with Advanced and Recurrent Colorectal Cancer","volume":"116","author":"Jones","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41698-022-00334-z","article-title":"Comprehensive Pan-Cancer Genomic Landscape of KRAS Altered Cancers and Real-World Outcomes in Solid Tumors","volume":"6","author":"Lee","year":"2022","journal-title":"NPJ Precis. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1056\/NEJMc2030638","article-title":"Distribution of KRAS G12C Somatic Mutations across Race, Sex, and Cancer Type","volume":"384","author":"Nassar","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.clcc.2020.04.009","article-title":"KRAS G12C Metastatic Colorectal Cancer: Specific Features of a New Emerging Target Population","volume":"19","author":"Schirripa","year":"2020","journal-title":"Clin. Color. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100567","DOI":"10.1016\/j.esmoop.2022.100567","article-title":"Clinical Efficacy of Sequential Treatments in KRASG12C-Mutant Metastatic Colorectal Cancer: Findings from a Real-Life Multicenter Italian Study (CRC-KR GOIM)","volume":"7","author":"Ciardiello","year":"2022","journal-title":"ESMO Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/oncolo\/oyac077","article-title":"Real-World Study of Characteristics and Treatment Outcomes Among Patients with KRAS p.G12C-Mutated or Other KRAS Mutated Metastatic Colorectal Cancer","volume":"27","author":"Fakih","year":"2022","journal-title":"Oncologist"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41591-023-02240-8","article-title":"Codon-Specific KRAS Mutations Predict Survival Benefit of Trifluridine\/Tipiracil in Metastatic Colorectal Cancer","volume":"29","author":"Ma","year":"2023","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.trecan.2023.07.010","article-title":"Next Batter up! Targeting Cancers with KRAS-G12D Mutations","volume":"9","author":"Zeissig","year":"2023","journal-title":"Trends Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1021\/pr501191a","article-title":"Differential Reprogramming of Isogenic Colorectal Cancer Cells by Distinct Activating KRAS Mutations","volume":"14","author":"Hammond","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cels.2019.07.006","article-title":"Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation","volume":"9","author":"Brubaker","year":"2019","journal-title":"Cell Syst."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13046-021-02225-w","article-title":"The Path to the Clinic: A Comprehensive Review on Direct KRASG12C Inhibitors","volume":"41","author":"Kwan","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100745","DOI":"10.1016\/j.esmoop.2022.100745","article-title":"Targeting KRASG12C in Colorectal Cancer: The Beginning of a New Era","volume":"8","author":"Ciardiello","year":"2023","journal-title":"ESMO Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nature12796","article-title":"K-Ras(G12C) Inhibitors Allosterically Control GTP Affinity and Effector Interactions","volume":"503","author":"Ostrem","year":"2013","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1021\/acsmedchemlett.8b00576","article-title":"Inhibitors of G12C Mutant Ras Proteins for the Treatment of Cancers","volume":"10","author":"Kargbo","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1126\/science.aad6204","article-title":"Cancer Therapeutics: Allele-Specific Inhibitors Inactivate Mutant KRAS G12C by a Trapping Mechanism","volume":"351","author":"Lito","year":"2016","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1158\/2159-8290.CD-15-1105","article-title":"Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State","volume":"6","author":"Patricelli","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-019-1694-1","article-title":"The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity","volume":"575","author":"Canon","year":"2019","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1917239","article-title":"KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors","volume":"383","author":"Hong","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1470-2045(21)00605-7","article-title":"Sotorasib for Previously Treated Colorectal Cancers with KRASG12C Mutation (CodeBreaK100): A Prespecified Analysis of a Single-Arm, Phase 2 Trial","volume":"23","author":"Fakih","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1200\/JCO.22.02524","article-title":"Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non\u2013Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100","volume":"41","author":"Dy","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1200\/JCO.21.02752","article-title":"First-in-Human Phase I\/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients with Advanced KRAS G12CSolid Tumors (KRYSTAL-1)","volume":"40","author":"Ou","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1056\/NEJMoa2212419","article-title":"Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C","volume":"388","author":"Yaeger","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ND11","DOI":"10.1158\/1538-7445.AM2022-ND11","article-title":"Discovery of GDC-6036, a Clinical Stage Treatment for KRAS G12C-Positive Cancers","volume":"82","author":"Purkey","year":"2022","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1056\/NEJMoa2303810","article-title":"Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation","volume":"389","author":"Sacher","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1200\/JCO.2023.41.16_suppl.3586","article-title":"Efficacy and Safety of IBI351 (GFH925) Monotherapy in Metastatic Colorectal Cancer Harboring KRASG12C Mutation: Preliminary Results from a Pooled Analysis of Two Phase I Studies","volume":"41","author":"Yuan","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S410","DOI":"10.1016\/j.annonc.2023.09.1741","article-title":"550O Safety and Efficacy of D-1553 in Combination with Cetuximab in KRAS G12C Mutated Colorectal Cancer (CRC): A Phase II Study","volume":"34","author":"Xu","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1158\/2159-8290.CD-20-0187","article-title":"EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer","volume":"10","author":"Amodio","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"110993","DOI":"10.1016\/j.celrep.2022.110993","article-title":"KRASG12C-Independent Feedback Activation of Wild-Type RAS Constrains KRASG12C Inhibitor Efficacy","volume":"39","author":"Ryan","year":"2022","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102343","DOI":"10.1016\/j.coph.2022.102343","article-title":"KRAS Inhibition in Metastatic Colorectal Cancer: An Update","volume":"68","author":"Nusrat","year":"2023","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41591-023-02717-6","article-title":"Sotorasib with Panitumumab in Chemotherapy-Refractory KRASG12C-Mutated Colorectal Cancer: A Phase 1b Trial","volume":"30","author":"Kuboki","year":"2024","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1056\/NEJMoa2308795","article-title":"Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C","volume":"389","author":"Fakih","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1200\/JCO.2023.41.16_suppl.3513","article-title":"Sotorasib (Soto) plus Panitumumab (Pmab) and FOLFIRI for Previously Treated KRAS G12C-Mutated Metastatic Colorectal Cancer (MCRC): CodeBreaK 101 Phase 1b Safety and Efficacy","volume":"41","author":"Hong","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41591-023-02696-8","article-title":"Divarasib plus Cetuximab in KRAS G12C-Positive Colorectal Cancer: A Phase 1b Trial","volume":"30","author":"Desai","year":"2024","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1073\/pnas.1812963116","article-title":"Discovery of Potent SOS1 Inhibitors That Block RAS Activation via Disruption of the RAS\u2013SOS1 Interaction","volume":"116","author":"Hillig","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.jtho.2023.09.151","article-title":"MA06.03 KontRASt-01: Preliminary Safety and Efficacy of JDQ443 + TNO155 in Patients with Advanced, KRAS G12C-Mutated Solid Tumors","volume":"18","author":"Negrao","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1158\/1078-0432.CCR-19-3523","article-title":"Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KrasG12C Inhibition","volume":"26","author":"Ryan","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1158\/1535-7163.MCT-22-0411","article-title":"Efficacious Combination Drug Treatment for Colorectal Cancer That Overcomes Resistance to KRAS G12C Inhibitors","volume":"22","author":"Matsubara","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"CT242","DOI":"10.1158\/1538-7445.AM2022-CT242","article-title":"Abstract CT242: KRYSTAL-16: A Phase I\/Ib Trial of Adagrasib (MRTX849) in Combination with Palbociclib in Patients with Advanced Solid Tumors with KRASG12C Mutation","volume":"82","author":"Sommerhalder","year":"2022","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1158\/2159-8290.CD-19-1167","article-title":"The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients","volume":"10","author":"Hallin","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2100250","DOI":"10.1002\/advs.202100250","article-title":"Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK\u2013YAP Signaling","volume":"8","author":"Zhang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/oncolo\/oyab080","article-title":"Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation","volume":"27","author":"Wang","year":"2022","journal-title":"Oncologist"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/2159-8290.CD-22-0158","article-title":"Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRAS G12C","volume":"12","author":"Weiss","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1056\/NEJMoa2105281","article-title":"Acquired Resistance to KRAS G12C Inhibition in Cancer","volume":"384","author":"Awad","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"ND07","DOI":"10.1158\/1538-7445.AM2023-ND07","article-title":"Abstract ND07: Discovery of RMC-6291, a Tri-Complex KRASG12C(ON) Inhibitor","volume":"83","author":"Cregg","year":"2023","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S410","DOI":"10.1016\/j.annonc.2023.09.1740","article-title":"549O Adagrasib with or without Cetuximab in Patients with KRASG12C-Mutated Colorectal Cancer (CRC): Analysis of Tumor Biomarkers and Genomic Alterations","volume":"34","author":"Pelster","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S373","DOI":"10.1016\/j.annonc.2022.04.437","article-title":"SO-39 Evaluation of Acquired Resistance to Sotorasib in KRAS p.G12C-Mutated Colorectal Cancer: Exploratory Plasma Biomarker Analysis of CodeBreaK 100","volume":"33","author":"Prenen","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1158\/2159-8290.CD-22-0405","article-title":"Molecular Characterization of Acquired Resistance to KRASG12C\u2013EGFR Inhibition in Colorectal Cancer","volume":"13","author":"Yaeger","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1158\/2159-8290.CD-21-0365","article-title":"Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS\u2013MAPK Reactivation","volume":"11","author":"Tanaka","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ccell.2024.01.012","article-title":"Adeno-to-Squamous Transition Drives Resistance to KRAS Inhibition in LKB1 Mutant Lung Cancer","volume":"42","author":"Tong","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/2159-8290.CD-11-0341","article-title":"EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib","volume":"2","author":"Corcoran","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature10868","article-title":"Unresponsiveness of Colon Cancer to BRAF(V600E) Inhibition through Feedback Activation of EGFR","volume":"483","author":"Prahallad","year":"2012","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"346ra92","DOI":"10.1126\/scitranslmed.aaf6219","article-title":"Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer","volume":"8","author":"Tie","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nm.2609","article-title":"Identification of a Mutation in the Extracellular Domain of the Epidermal Growth Factor Receptor Conferring Cetuximab Resistance in Colorectal Cancer","volume":"18","author":"Montagut","year":"2012","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e175245","DOI":"10.1001\/jamaoncol.2017.5245","article-title":"Efficacy of Sym004 in Patients With Metastatic Colorectal Cancer With Acquired Resistance to Anti-EGFR Therapy and Molecularly Selected by Circulating Tumor DNA Analyses: A Phase 2 Randomized Clinical Trial","volume":"4","author":"Montagut","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.annonc.2023.02.016","article-title":"Plasmatic BRAF-V600E Allele Fraction as a Prognostic Factor in Metastatic Colorectal Cancer Treated with BRAF Combinatorial Treatments","volume":"34","author":"Ros","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/annonc\/mdy509","article-title":"Anti-EGFR-Resistant Clones Decay Exponentially after Progression: Implications for Anti-EGFR Re-Challenge","volume":"30","author":"Parseghian","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamaoncol.2019.0528","article-title":"Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer","volume":"5","author":"Reinert","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1038\/s41591-022-01886-0","article-title":"Circulating Tumor DNA to Guide Rechallenge with Panitumumab in Metastatic Colorectal Cancer: The Phase 2 CHRONOS Trial","volume":"28","author":"Pietrantonio","year":"2022","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.clcc.2021.12.001","article-title":"Rechallenge With BRAF and Anti-EGFR Inhibitors in Patients With Metastatic Colorectal Cancer Harboring BRAFV600E Mutation Who Progressed on Cetuximab and Encorafenib With or Without Binimetinib: A Case Series","volume":"21","author":"Ji","year":"2022","journal-title":"Clin. Color. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.annonc.2023.10.120","article-title":"Circulating Tumor DNA, and Clinical Features to Guide Rechallenge with BRAF Inhibitors in BRAF-V600E Mutated Metastatic Colorectal Cancer","volume":"35","author":"Ros","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1200\/PO.21.00107","article-title":"Targeting Secondary and Tertiary Resistance to BRAF Inhibition in BRAF V600E\u2013Mutated Metastatic Colorectal Cancer","volume":"5","author":"Akhoundova","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tim.2022.08.010","article-title":"Fusobacterium Nucleatum, a Key Pathogenic Factor and Microbial Biomarker for Colorectal Cancer","volume":"31","author":"Wang","year":"2023","journal-title":"Trends Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1200\/JCO.2023.41.16_suppl.3534","article-title":"Gut Microbiome Composition as Predictor of the Efficacy of Adding Atezolizumab to First-Line FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer: A Translational Analysis of the AtezoTRIBE Study","volume":"41","author":"Marmorino","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1038\/s41467-024-45572-w","article-title":"Fusobacterium Nucleatum Promotes Tumor Progression in KRAS p.G12D-Mutant Colorectal Cancer by Binding to DHX15","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:13:45Z","timestamp":1760105625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,14]]},"references-count":70,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063304"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,14]]}}}