{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:46:56Z","timestamp":1782798416964,"version":"3.54.5"},"reference-count":167,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Oncogenic KRAS mutations are the most common driver event in NSCLC, occurring in up to 30% of patients. Direct strategies to target KRAS (and other RAS isoforms) met with consistent failure until the discovery of covalent KRAS G12C inhibitors, leading to a first-in-class FDA accelerated approval for the treatment of NSCLC in 2021. Since then, multiple chemotypes have been reported to extend direct KRAS targeting beyond G12C alleles, with several dozen molecules entering early or late clinical testing in rapid succession. Here, we review such strategies. We recap the chemistry and clinical strategy behind G12C inhibitors as a first step in direct KRAS targeting. We then propose an overarching classification schema for novel KRAS targeting molecules, focusing on the chemical strategies encoded in their use, and moving beyond conventional inhibitors to glues, degraders, and other novel pharmacologies. We evaluate the non-G12C, allele-specific molecules (such as those targeting G12D), inhibitors of multiple KRAS alleles (\u201cpan-KRAS\u201d) and inhibitors of all RAS isoforms (\u201cpan-RAS\u201d). We consider these molecules\u2019 potential as monotherapy, in combination with one another, and in combination with conventional (FDA-approved) or novel (unapproved) treatments. Finally, we discuss what the future may hold for KRAS directed strategies in NSCLC.<\/jats:p>","DOI":"10.3389\/fonc.2026.1817943","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:40:00Z","timestamp":1782798000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic inhibition of RAS in non-small cell lung cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Katherine B.","family":"Nichols","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Columbia University Irving Medical Center","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin O.","family":"Herzberg","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Columbia University Irving Medical Center","place":["New York, NY, United States"]},{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/292506a0","article-title":"The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes","volume":"292","author":"Ellis","year":"1981","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/300149a0","article-title":"A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene","volume":"300","author":"Reddy","year":"1982","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/300143a0","article-title":"Mechanism of activation of a human oncogene","volume":"300","author":"Tabin","year":"1982","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.042","article-title":"It took a long, long time: Ras and the race to cure cancer","volume":"187","author":"Weinberg","year":"2024","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1097","article-title":"RAS oncogenes: the first 30 years","volume":"3","author":"Malumbres","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-4023","article-title":"Treatment outcomes and clinical characteristics of patients with KRAS-G12C\u2013mutant non\u2013small cell lung canceroutcomes of patients with KRAS-G12C\u2013mutant lung cancer","volume":"27","author":"Arbour","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00671-9","article-title":"The current state of the art and future trends in RAS-targeted cancer therapies","volume":"19","author":"Punekar","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/edbk_360354","article-title":"Overcoming KRAS -mutant lung cancer","volume":"42","author":"Luo","year":"2022","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-21-1331","article-title":"Expanding the reach of precision oncology by drugging all KRAS mutants","volume":"12","author":"Hofmann","year":"2022","journal-title":"Cancer Discov"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(09)70155-x","article-title":"Molecular predictive and prognostic markers in non-small-cell lung cancer","volume":"10","author":"Le","year":"2009","journal-title":"Lancet Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1504688","article-title":"Clinical implications of genomic discoveries in lung cancer","volume":"374","author":"S","year":"2016","journal-title":"N Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-21-0201","article-title":"Characterization of KRAS mutation subtypes in non-small cell lung cancer","volume":"20","author":"J","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"B14","doi-asserted-by":"publisher","first-page":"8567","DOI":"10.1200\/jco.2024.42.16_suppl.8567","article-title":"Evaluation of the genomic and immune profiles of patients with lung adenosquamous carcinoma (LUAS) and association of response to treatment","volume":"42","author":"Lee","year":"2024","journal-title":"J Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00733-6","article-title":"Rare molecular subtypes of lung cancer","volume":"20","author":"Harada","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","article-title":"Oncogenic signaling pathways in The Cancer Genome Atlas","volume":"173","author":"Sanchez-Vega","year":"2018","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","article-title":"RAS proteins and their regulators in human disease","volume":"170","author":"S","year":"2017","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.mcr-15-0203","article-title":"Biochemical and structural analysis of common cancer-associated KRAS mutations","volume":"13","author":"Hunter","year":"2015","journal-title":"Mol Cancer Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.182873","article-title":"RAS isoforms and mutations in cancer at a glance","volume":"129","author":"Hobbs","year":"2016","journal-title":"J Cell Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.2821624","article-title":"A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants","volume":"238","author":"Trahey","year":"1987","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90149-9","article-title":"The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae","volume":"63","author":"Xu","year":"1990","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/351576a0","article-title":"Differential regulation of rasGAP and neurofibromatosis gene product activities","volume":"351","author":"Bollag","year":"1991","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0997-686","article-title":"Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras","volume":"4","author":"A","year":"1997","journal-title":"Nat Struct Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.333","article-title":"The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants","volume":"277","author":"S","year":"1997","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-22-1731","article-title":"Genomic landscapes and hallmarks of mutant RAS in human cancers","volume":"82","author":"Scharpf","year":"2022","journal-title":"Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-11-2612","article-title":"A comprehensive survey of Ras mutations in cancer","volume":"72","author":"Prior","year":"2012","journal-title":"Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-08-0646","article-title":"Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma","volume":"14","author":"Riely","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-11-3265","article-title":"Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers","volume":"18","author":"Dogan","year":"2012","journal-title":"Am Assoc Cancer Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2019.08.61","article-title":"Differences in molecular epidemiology of lung cancer among ethnicities (Asian vs. Caucasian)","volume":"12","author":"Izumi","year":"2019","journal-title":"J Thorac Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-20-455","article-title":"KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples","volume":"9","author":"Loong","year":"2020","journal-title":"Transl Lung Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/po.21.00245","article-title":"Landscape of KRASG12C, associated genomic alterations, and interrelation with immuno-oncology biomarkers in KRAS-mutated cancers","volume":"6","author":"Salem","year":"2022","journal-title":"JCO Precis Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.07.005","article-title":"Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRAS G12D-mutated non-small-cell lung cancer","volume":"33","author":"Ricciuti","year":"2022","journal-title":"Ann Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2022.100390","article-title":"Clinicopathologic characteristics and outcomes for patients with KRAS G12D-mutant NSCLC","volume":"3","author":"C","year":"2022","journal-title":"JTO Clin Res Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"8618","DOI":"10.1200\/jco.2024.42.16_suppl.8618","article-title":"Molecular and clinical characteristics of patients with non-small-cell lung cancer (NSCLC) harboring KRAS G12V mutations","volume":"42","author":"John","year":"2024","journal-title":"J Clin Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2021.100261","article-title":"Clinical characteristics and outcomes in advanced KRAS-mutated NSCLC: a multicenter collaboration in Asia (ATORG-005)","volume":"3","author":"Lee","year":"2022","journal-title":"JTO Clin Res Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature05945","article-title":"Identification of the transforming EML4\u2013ALK fusion gene in non-small-cell lung cancer","volume":"448","author":"Soda","year":"2007","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00515-0","article-title":"ALK-positive lung cancer: a moving target","volume":"4","author":"Schneider","year":"2023","journal-title":"Nat Cancer"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nature13385","article-title":"Comprehensive molecular profiling of lung adenocarcinoma","volume":"511","author":"Collisson","year":"2014","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.63.4600","article-title":"MET exon 14 mutations in non\u2013small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression","volume":"34","author":"Awad","year":"2016","journal-title":"J Clin Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-4772","article-title":"KRASG12C mutation is associated with increased risk of recurrence in surgically resected lung adenocarcinomakrasg12c and genomic correlates in lung adenocarcinoma","volume":"27","author":"Jones","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"9088","DOI":"10.1200\/jco.2021.39.15_suppl.9088","article-title":"Chemo-immunotherapy outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer","volume":"39","author":"Arbour","year":"2021","journal-title":"J Clin Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-2719","article-title":"Comparative analysis and isoform-specific therapeutic vulnerabilities of KRAS mutations in non-small cell lung cancer","volume":"28","author":"Ricciuti","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17594","article-title":"Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: a meta-analysis and review","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"B45","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1001\/jamaoncol.2017.4427","article-title":"Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non\u2013small cell lung carcinoma: a systematic review and meta-analysis","volume":"4","author":"Lee","year":"2017","journal-title":"JAMA Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1097\/jto.0000000000000432","article-title":"Prognostic impact of KRAS mutation subtypes in 677 patients with metastatic lung adenocarcinomas","volume":"10","author":"Yu","year":"2015","journal-title":"J Thorac Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-3771","article-title":"A blood-based assay for assessment of tumor mutational burden in first-line metastatic NSCLC treatment: results from the MYSTIC study","volume":"27","author":"Si","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-22-1420","article-title":"Co-mutations and KRAS G12C inhibitor efficacy in advanced NSCLC","volume":"13","author":"Negrao","year":"2023","journal-title":"Cancer Discov"},{"key":"B49","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41568-019-0179-8","article-title":"Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy","volume":"19","author":"Skoulidis","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"B50","doi-asserted-by":"publisher","first-page":"9039","DOI":"10.1200\/jco.2023.41.16_suppl.9039","article-title":"Effects of mutations in SWI\/SNF subunits on context-specific prognosis in driver positive and driver negative NSCLC","volume":"41","author":"Herzberg","year":"2023","journal-title":"J Clin Oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.03.024","article-title":"Smarca4 and other SWItch\/Sucrose NonFermentable family genomic alterations in NSCLC: Clinicopathologic characteristics and outcomes to immune checkpoint inhibition","volume":"16","author":"Alessi","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.jtho.2021.10.013","article-title":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","volume":"17","author":"Ricciuti","year":"2022","journal-title":"J Thorac Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2024.107510","article-title":"Outcomes in patients treated with frontline immune checkpoint inhibition (ICI) for advanced NSCLC with KRAS mutations and STK11\/KEAP1 comutations across PD-L1 levels","volume":"190","author":"Sun","year":"2024","journal-title":"Lung Cancer"},{"key":"B54","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA: A Cancer J Clin"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00542-z","article-title":"Advances in covalent drug discovery","volume":"21","author":"Boike","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad6204","article-title":"Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism","volume":"351","author":"Lito","year":"2016","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.cell.2018.01.006","article-title":"Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor","volume":"172","author":"Janes","year":"2018","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2103695","article-title":"Sotorasib for lung cancers with KRAS p.G12C mutation","volume":"384","author":"Skoulidis","year":"2021","journal-title":"New Engl J Med"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2210539","article-title":"Adagrasib in non\u2013small-cell lung cancer","volume":"387","author":"Kotecha","year":"2022","journal-title":"New Engl J Med"},{"key":"B60","doi-asserted-by":"publisher","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":"B61","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1200\/jco.2024.42.16_suppl.3007","article-title":"Pan-tumor activity of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in patients with KRAS G12C-mutant advanced solid tumors","volume":"42","author":"Heist","year":"2024","journal-title":"J Clin Oncol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(14)60845-x","article-title":"Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial","volume":"384","author":"Garon","year":"2014","journal-title":"Lancet"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)00221-0","article-title":"Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial","volume":"401","author":"Langen","year":"2023","journal-title":"Lancet"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)00866-9","article-title":"Adagrasib versus docetaxel in KRAS G12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial","volume":"406","author":"Barlesi","year":"2025","journal-title":"Lancet"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(11)70393-x","article-title":"Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial","volume":"13","author":"Rosell","year":"2012","journal-title":"Lancet Oncol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604249","article-title":"Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403)","volume":"98","author":"Tamura","year":"2008","journal-title":"Br J Cancer"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114204","article-title":"Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC","volume":"208","author":"Hochmair","year":"2024","journal-title":"Eur J Cancer"},{"key":"B68","doi-asserted-by":"publisher","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":"B69","doi-asserted-by":"publisher","DOI":"10.1056\/nejme2311611","article-title":"Combination therapy and appropriate dosing to target KRAS in colorectal cancer","volume":"389","author":"Yaeger","year":"2023","journal-title":"N Engl J Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2024.09.629","article-title":"P3.12D.07 Divarasib versus adagrasib or sotorasib in pretreated KRAS G12C+ advanced or metastatic non-small cell lung cancer (NSCLC)","volume":"19","author":"Gadgeel","year":"2024","journal-title":"J Thorac Oncol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1200\/po.23.00030","article-title":"Clinical and genomic features of response and toxicity to sotorasib in a real-world cohort of patients with advanced KRAS G12C-mutant non-small cell lung cancer","volume":"7","author":"Thummalapalli","year":"2023","journal-title":"JCO Precis Oncol"},{"key":"B72","article-title":"Mutations in SWI\/SNF subunits have context-specific prognostic effects in driver subsets of NSCLC","author":"Herzberg","year":""},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-20-1825","article-title":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","volume":"26","author":"Schoenfeld","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.08.010","article-title":"KEAP1 and TP53 frame genomic, evolutionary, and immunologic subtypes of lung adenocarcinoma with different sensitivity to immunotherapy","volume":"16","author":"Scalera","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1200\/jco.23.00580","article-title":"Genomic and immunophenotypic landscape of acquired resistance to PD-(L)1 blockade in non\u2013small-cell lung cancer","volume":"42","author":"Ricciuti","year":"2024","journal-title":"J Clin Oncol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2105281","article-title":"Acquired resistance to KRASG12C inhibition in cancer","volume":"384","author":"Awad","year":"2021","journal-title":"New Engl J Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04065-2","article-title":"Diverse alterations associated with resistance to KRAS(G12C) inhibition","volume":"599","author":"Zhao","year":"2021","journal-title":"Nature"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.01.020","article-title":"Genomic landscape of clinically acquired resistance alterations in patients treated with KRASG12C inhibitors","volume":"36","author":"Riedl","year":"2025","journal-title":"Ann Oncol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-22-0405","article-title":"Molecular characterization of acquired resistance to KRAS G12C-EGFR inhibition in colorectal cancer","volume":"13","author":"Yaeger","year":"2022","journal-title":"Cancer Discov"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-12-2246","article-title":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","volume":"19","author":"Yu","year":"2013","journal-title":"Clin Cancer Res"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-14-0337","article-title":"AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer","volume":"4","author":"Cross","year":"2014","journal-title":"Cancer Discov"},{"key":"B82","doi-asserted-by":"publisher","first-page":"75ra26","DOI":"10.1126\/scitranslmed.3002003","article-title":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","volume":"3","author":"Sequist","year":"2011","journal-title":"Sci Transl Med"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx703","article-title":"Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors","volume":"29","author":"Westover","year":"2018","journal-title":"Ann Oncol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0573-8","article-title":"Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer","volume":"121","author":"Leonetti","year":"2019","journal-title":"Brit J Cancer"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.10.689","article-title":"977MO Safety and efficacy of elironrasib, a RAS(ON) G12C-selective inhibitor, in previously treated patients with KRAS G12C NSCLC","volume":"36","author":"Tan","year":"2025","journal-title":"Ann Oncol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2212419","article-title":"Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C","author":"Yaeger","year":"2022","journal-title":"New Engl J Med"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.targ-21-p05-01","article-title":"Abstract P05-01: A phase 1b study evaluating the safety and efficacy of sotorasib, a KRASG12C inhibitor, in combination with trametinib, a MEK inhibitor, in KRAS p.G12C-mutated solid tumors","volume":"20","author":"Ramalingam","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2022.07.022","article-title":"OA03.03 Sotorasib in combination with RMC-4630, a SHP2 inhibitor, in KRAS p.G12C-mutated NSCLC and other solid tumors","volume":"17","author":"Falchook","year":"2022","journal-title":"J Thorac Oncol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.targ-21-p05-02","article-title":"Abstract P05-02: A phase 1b study evaluating the combination of sotorasib, a KRASG12C inhibitor, and afatinib, a pan-ErbB tyrosine kinase inhibitor, in advanced KRAS p.G12C mutated non-small cell lung cancer (NSCLC)","volume":"20","author":"Gandara","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1380584","article-title":"KRAS G12C inhibitor combination therapies: current evidence and challenge","volume":"14","author":"Miyashita","year":"2024","journal-title":"Front Oncol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-24-0489","article-title":"Combined KRAS inhibition and immune therapy generates durable complete responses in an autochthonous PDAC model","volume":"15","author":"Liu","year":"2024","journal-title":"Cancer Discov"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.02.012","article-title":"Exploiting the therapeutic implications of KRAS inhibition on tumor immunity","volume":"42","author":"Molina-Arcas","year":"2024","journal-title":"Cancer Cell"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-22-3655","article-title":"Facts and hopes on RAS inhibitors and cancer immunotherapy","volume":"29","author":"Boumelha","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.ccell.2022.07.005","article-title":"A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy","volume":"40","author":"Zhang","year":"2022","journal-title":"Cancer Cell"},{"key":"B95","doi-asserted-by":"publisher","first-page":"8500","DOI":"10.1200\/jco.2025.43.16_suppl.8500","article-title":"First-line adagrasib (ADA) with pembrolizumab (PEMBRO) in patients (pts) with advanced\/metastatic KRAS G12C -mutated non-small cell lung cancer (NSCLC) from the phase 2 portion of the KRYSTAL-7 study","volume":"43","author":"J\u00e4nne","year":"2025","journal-title":"J Clin Oncol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.11.018","article-title":"Efficacy and safety of olomorasib in combination with pembrolizumab in treatment of patients with KRAS G12C-mutant advanced NSCLC","author":"Burns","year":"2025","journal-title":"J Thorac Oncol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2025.43.16_suppl.tps8656","article-title":"Krascendo 2: A phase III study of divarasib and pembrolizumab vs pembrolizumab and chemotherapy in patients with previously untreated, advanced or metastatic, KRAS G12C-mutated non-small cell lung cancer (NSCLC)","volume":"43","author":"Skoulidis","year":"2025","journal-title":"J Clin Oncol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2204619","article-title":"Adagrasib in non\u2013small-cell lung cancer harboring a KRASG12C mutation","volume":"387","author":"J\u00e4nne","year":"2022","journal-title":"New Engl J Med"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2021.100213","article-title":"Severe immune checkpoint inhibitor hepatitis in KRAS G12C-mutant NSCLC potentially triggered by sotorasib: Case report","volume":"2","author":"Begum","year":"2021","journal-title":"JTO Clin Res Rep"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105074","article-title":"Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: a comprehensive clinical and pharmacokinetic analysis","volume":"102","author":"Ernst","year":"2024","journal-title":"eBioMedicine"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-22-0383","article-title":"Activity of adagrasib (MRTX849) in brain metastases: Preclinical models and clinical data from patients with KRASG12C-mutant non-small cell lung cancer preliminary activity of adagrasib in brain metastases","volume":"28","author":"Sabari","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B102","doi-asserted-by":"publisher","first-page":"S1123","DOI":"10.1016\/j.jtho.2021.08.547","article-title":"P52.03 efficacy of sotorasib in KRAS p.G12C-mutated NSCLC with stable brain metastases: A post-hoc analysis of CodeBreaK 100","volume":"16","author":"Ramalingam","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2025.108683","article-title":"Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial","volume":"207","author":"Dingemans","year":"2025","journal-title":"Lung Cancer"},{"key":"B104","doi-asserted-by":"publisher","first-page":"3834","DOI":"10.1038\/s41467-026-69943-7","article-title":"Pan-tumor activity of olomorasib, a next-generation KRAS G12C inhibitor in KRAS G12C-mutant advanced solid tumors: A first-in-human study","volume":"17","author":"Murciano-Goroff","year":"2026","journal-title":"Nat Commun"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-24-0840","article-title":"Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C","volume":"15","author":"Meier","year":"2025","journal-title":"Cancer Discov"},{"key":"B106","doi-asserted-by":"publisher","first-page":"TPS3184","DOI":"10.1200\/jco.2024.42.16_suppl.tps3184","article-title":"Phase 1\/2 study of FMC-376 an oral KRAS G12C dual inhibitor in participants with locally advanced unresectable or metastatic solid tumors (PROSPER)","volume":"42","author":"Keating","year":"2024","journal-title":"J Clin Oncol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1158\/1538-7445.am2023-1142","article-title":"Abstract 1142: Discovery of FMC-376 a novel orally bioavailable inhibitor of activated KRASG12C","volume":"83","author":"Patel","year":"2023","journal-title":"Cancer Res"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.2297","article-title":"LBA55 mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: An early analysis from the phase III MARIPOSA study","volume":"35","author":"Besse","year":"2024","journal-title":"Ann Oncol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2502929","article-title":"First-line camizestrant for emerging ESR1-mutated advanced breast cancer","volume":"393","author":"Bidard","year":"2025","journal-title":"N Engl J Med"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.95","article-title":"Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase","volume":"4","author":"DuPage","year":"2009","journal-title":"Nat Protoc"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-025-01316-z","article-title":"Induced proximity-based therapeutic modalities","volume":"21","author":"King","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: The past is prologue","volume":"21","author":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B114","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41568-025-00817-8","article-title":"Targeted protein degradation for cancer therapy","volume":"25","author":"Hinterndorfer","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1056\/nejmp2208954","article-title":"The on- and off-ramps of oncology accelerated approval","volume":"387","author":"Fashoyin-Aje","year":"2022","journal-title":"N Engl J Med"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02007-7","article-title":"Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor","volume":"28","author":"Hallin","year":"2022","journal-title":"Nat Med"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01688","article-title":"Identification of MRTX1133, a noncovalent, potent, and selective KRASG12D inhibitor","volume":"65","author":"Wang","year":"2022","journal-title":"J Med Chem"},{"key":"B118","unstructured":"A phase 1\/2 multiple expansion cohort trial of MRTX1133 in patients with advanced solid tumors harboring a KRAS G12D mutation\n          \n          \n          \n          2025"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-23-2098","article-title":"A small molecule with big impact: MRTX1133 targets the KRASG12D mutation in pancreatic cancer","volume":"30","author":"Wang","year":"2024","journal-title":"Clin Cancer Res"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.ccell.2024.06.001","article-title":"Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer","volume":"42","author":"Zhou","year":"2024","journal-title":"Cancer Cell"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.08.1484","article-title":"915O KRAS G12D inhibitor HRS-4642 in patients with KRAS G12D-mutant advanced solid tumors: A phase I trial","volume":"36","author":"Xiong","year":"2025","journal-title":"Ann Oncol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.08.1485","article-title":"916O preliminary phase I results of INCB161734, a novel oral KRAS G12D inhibitor, in patients with advanced or metastatic solid tumors","volume":"36","author":"Desai","year":"2025","journal-title":"Ann Oncol"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.09.110","article-title":"MA02.07 efficacy and safety of GFH375 in advanced non-small cell lung cancer patients with KRAS G12D mutation","volume":"20","author":"Lu","year":"2025","journal-title":"J Thorac Oncol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s42004-025-01662-4","article-title":"Discovery of KRAS(G12D) selective degrader ASP3082","volume":"8","author":"Tanaka","year":"2025","journal-title":"Commun Chem"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.675","article-title":"Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic, colorectal, and non-small cell lung cancer","volume":"35","author":"Wang","year":"2024","journal-title":"Ann Oncol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2600752","article-title":"Setidegrasib in advanced non\u2013small-cell lung cancer and pancreatic cancer","volume":"394","author":"Park","year":"2026","journal-title":"N Engl J Med"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.targ-25-b107","article-title":"Abstract B107: Preclinical activity of ARV-806, a PROTAC KRAS G12D degrader","volume":"24","author":"Smith","year":"2025","journal-title":"Mol Cancer Ther"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2026.44.2_suppl.tps792","article-title":"Phase 1\/2 study of ARV-806, a PROTAC KRAS G12D degrader, in KRAS G12D\u2013mutated advanced solid tumors, including pancreatic cancer","volume":"44","author":"Murciano-Goroff","year":"2026","journal-title":"J Clin Oncol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.targ-25-a063","article-title":"Abstract A063: BBO-11818: an orally bioavailable, highly potent and selective non-covalent pan-KRAS(ON) and (OFF) inhibitor with robust anti-tumor activity in KRAS-mutant preclinical models","volume":"24","author":"Stahlhut","year":"2025","journal-title":"Mol Cancer Ther"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.am2025-4375","article-title":"LY4066434, an oral small molecule pan-KRAS inhibitor, demonstrates robust anti-tumor activity in KRAS-mutant models, including in the CNS","volume":"85","author":"Huang","year":"2025","journal-title":"Cancer Res"},{"key":"B131","doi-asserted-by":"publisher","first-page":"S661","DOI":"10.1016\/j.annonc.2025.08.1585","article-title":"1016eTiP a first-in-human phase I study of LY4066434, a potent and orally bioavailable pan-KRAS inhibitor, in KRAS-mutant solid tumors (trial in progress)","volume":"36","author":"Kitano","year":"2025","journal-title":"Ann Oncol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114537","article-title":"8 oral: ALTA3263: an oral, KRAS isoform-selective, dual ON\/OFF state, noncovalent inhibitor induces regressions across KRAS G12V, G12D, and G12C cancer models","volume":"211","author":"Wang","year":"2024","journal-title":"Eur J Cancer"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-24-0386","article-title":"Pan-KRAS inhibitors BI-2493 and BI-2865 display potent anti-tumor activity in tumors with KRAS wild-type allele amplification","author":"Tedeschi","year":"2024","journal-title":"Mol Cancer Ther"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06123-3","article-title":"Pan-KRAS inhibitor disables oncogenic signalling and tumour growth","volume":"619","author":"Kim","year":"2023","journal-title":"Nature"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3122478\/v1","article-title":"Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy","author":"Singh","year":"2023"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07379-z","article-title":"Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer","volume":"629","author":"Wasko","year":"2024","journal-title":"Nature"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08283-2","article-title":"Pharmacologic restoration of GTP hydrolysis by mutant RAS","volume":"637","author":"Cuevas-Navarro","year":"2024","journal-title":"Nature"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1016\/s1556-0864(25)00201-1","article-title":"6MO: Safety and clinical activity of daraxonrasib (RMC-6236) in RAS mutant non-small cell lung cancer (NSCLC)","volume":"20","author":"Punekar","year":"2025","journal-title":"J Thorac Oncol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c01441","article-title":"RAS(ON) therapies on the horizon to address KRAS resistance: Highlight on a phase III clinical candidate daraxonrasib (RMC-6236)","volume":"68","author":"Zhang","year":"2025","journal-title":"J Med Chem"},{"key":"B140","doi-asserted-by":"publisher","first-page":"S458","DOI":"10.1016\/j.annonc.2023.09.1838","article-title":"652O preliminary clinical activity of RMC-6236, a first-in-class, RAS-selective, tri-complex RAS-MULTI(ON) inhibitor in patients with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC)","volume":"34","author":"Arbour","year":"2023","journal-title":"Ann Oncol"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2505783","article-title":"Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer","volume":"394","author":"Wolpin","year":"2026","journal-title":"N Engl J Med"},{"key":"B142","doi-asserted-by":"publisher","first-page":"TPS4230","DOI":"10.1200\/jco.2025.43.16_suppl.tps4230","article-title":"Trial in progress: RASolute 302\u2014a phase 3, multicenter, global, open-label, randomized study of daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, versus standard of care chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC)","volume":"43","author":"Wolpin","year":"2025","journal-title":"J Clin Oncol"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2025.09.1080","article-title":"P3.18.65 trial in progress - RAsolve 301: A phase 3 study of daraxonrasib (RMC-6236) vs. docetaxel in in patients with previously treated RAS mutant NSCLC","volume":"20","author":"Skoulidis","year":"2025","journal-title":"J Thorac Oncol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1970","article-title":"Mechanisms of cutaneous toxicities to EGFR inhibitors","volume":"6","author":"Lacouture","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.am2025-4367","article-title":"ERAS-4001 is a pan-KRAS inhibitor with robust anti-tumor activity in KRAS altered solid tumors","volume":"85","author":"Brown","year":"2025","journal-title":"Cancer Res"},{"key":"B146","unstructured":"A phase 1 first-in-human open-label study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of ERAS-4001 monotherapy and in combination in patients with advanced solid tumors\n          \n          \n          \n          2025"},{"key":"B147","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.1158\/1538-7445.am2022-3595","article-title":"Abstract 3595: RMC-6291, a next-generation tri-complex KRASG12C(ON) inhibitor, outperforms KRASG12C(OFF) inhibitors in preclinical models of KRASG12C cancers","volume":"82","author":"Nichols","year":"2022","journal-title":"Cancer Res"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.targ-23-pr014","article-title":"Abstract PR014: Preliminary safety and anti-tumor activity of RMC-6291, a first-in-class, tri-complex KRASG12C(ON) inhibitor, in patients with or without prior KRASG12C(OFF) inhibitor treatment","volume":"22","author":"J\u00e4nne","year":"2023","journal-title":"Mol Cancer Ther"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-25-0600","article-title":"RAS-GTP inhibition overcomes acquired resistance to KRASG12C inhibitors mediated by oncogenic and wildtype RAS activation in non-small cell lung cancer","author":"Solanki","year":"2025","journal-title":"Cancer Res"},{"key":"B150","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1200\/jco.2025.43.4_suppl.724","article-title":"Preliminary safety, antitumor activity, and circulating tumor DNA (ctDNA) changes with RMC-9805, an oral, RAS(ON) G12D-selective tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors","volume":"43","author":"Spira","year":"2025","journal-title":"J Clin Oncol"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.am2025-ct019","article-title":"Abstract CT019: Preliminary safety and antitumor activity of zoldonrasib (RMC-9805), an oral, RAS(ON) G12D-selective, tri-complex inhibitor in patients with KRAS G12D non-small cell lung cancer (NSCLC) from a phase 1 study in advanced solid tumors","volume":"85","author":"Arbour","year":"2025","journal-title":"Cancer Res"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.am2025-nd06","article-title":"Abstract ND06: Discovery of RMC-5127, an oral, RAS (ON) G12V-selective, noncovalent, tri-complex inhibitor","volume":"85","author":"Edwards","year":"2025","journal-title":"Cancer Res"},{"key":"B153","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/jnci\/djaf236","article-title":"The impact of eligibility criteria on Kirsten rat sarcoma G12C inhibitor trials in patients with non\u2013small cell lung cancer","volume":"118","author":"Wooster","year":"2025","journal-title":"JNCI: J Natl Cancer Inst"},{"key":"B154","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1016\/j.cell.2017.11.009","article-title":"Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy","volume":"171","author":"Palmer","year":"2017","journal-title":"Cell"},{"key":"B155","doi-asserted-by":"publisher","first-page":"candisc.0212.2021","DOI":"10.1158\/2159-8290.cd-21-0212","article-title":"Independent drug action in combination therapy: Implications for precision oncology","volume":"12","author":"Plana","year":"2022","journal-title":"Cancer Discov"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2306434","article-title":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","volume":"389","author":"Planchard","year":"2023","journal-title":"N Engl J Med"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.24.649345","article-title":"Mechanisms of resistance to active state selective tri-complex RAS inhibitors","author":"Sang","year":"2025","journal-title":"bioRxiv"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-24-0177","article-title":"Mechanisms of resistance to oncogenic KRAS inhibition in pancreatic cancer","volume":"14","author":"Dilly","year":"2024","journal-title":"Cancer Discov"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non\u2013small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348","article-title":"Mutational landscape determines sensitivity to PD-1 blockade in non\u2013small cell lung cancer","volume":"348","author":"Rizvi","year":"2015","journal-title":"Science"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09219-0","article-title":"The mutagenic forces shaping the genomes of lung cancer in never smokers","volume":"644","author":"D\u00edaz-Gay","year":"2025","journal-title":"Nature"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114979","article-title":"501LBA LBA Orals: Phase 1 expansion results of IDE397, a first-in-class, oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell lung cancer (NSCLC) and urothelial cancer (UC)","volume":"211","author":"Herzberg","year":"2024","journal-title":"Eur J Cancer"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.2339","article-title":"First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase I dose exploration \u2729","volume":"35","author":"Rodon","year":"2024","journal-title":"Ann Oncol"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-23-0669","article-title":"MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP deleted cancer","author":"Engstrom","year":"2023","journal-title":"Cancer Discov"},{"key":"B166","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1158\/1538-7445.am2025-6737","article-title":"Abstract 6737: RAS inhibitors as payloads of ADCs to treat RAS-mutant tumors","volume":"85","author":"Zhong","year":"2025","journal-title":"Cancer Res"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1136\/bmjonc-2025-001037","article-title":"Human and financial consequences of herding in oncology drug development: clinical trials of TIGIT inhibitors","volume":"5","author":"Zhang","year":"2026","journal-title":"BMJ Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1817943\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:40:11Z","timestamp":1782798011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1817943\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":167,"alternative-id":["10.3389\/fonc.2026.1817943"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1817943","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"article-number":"1817943"}}