{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:16:32Z","timestamp":1779387392829,"version":"3.53.1"},"reference-count":92,"publisher":"Informa UK Limited","issue":"12","funder":[{"name":"National Institute of Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA240607"],"award-info":[{"award-number":["R01CA240607"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["Expert Opinion on Investigational Drugs"],"published-print":{"date-parts":[[2025,12,2]]},"DOI":"10.1080\/13543784.2025.2611395","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:46:49Z","timestamp":1767808009000},"page":"1011-1021","update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":1,"title":["An overview of KRAS-targeting therapies for colorectal cancer in phase I and II development"],"prefix":"10.1080","volume":"34","author":[{"given":"Shadi","family":"Chamseddine","sequence":"first","affiliation":[{"name":"Wayne State University","place":["Detroit, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asfar","family":"Azmi","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine","place":["Detroit, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Wasif","family":"Saif","sequence":"additional","affiliation":[{"name":"Barbara Ann Karmanos Cancer Institute","place":["Detroit, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"301","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.5114\/pg.2018.81072"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.102882"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12091534"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3967"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.04.002"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.182873"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8454"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2406906"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2005.06.003"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-019-03344-9"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.37"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804385"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw261"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2018-000353"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26352"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-15-0203"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12796"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-1105"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad6204"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1694-1"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01180"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.9.3035-3045.2002"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13213"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01688"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01629-x"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.08.016"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12999"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5004"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02363-1"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm9010012"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11156"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.3797"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2018.05.012"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02717-6"},{"key":"e_1_3_4_37_1","unstructured":"A Phase 2 Open-label multicenter study of the combination of RMC-4630 and sotorasib for non-small cell lung cancer subjects with KRASG12C mutation after failure of prior standard therapies [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05054725"},{"key":"e_1_3_4_38_1","unstructured":"A Phase 1\/2 study of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C mutant non-small cell lung cancer (NSCLC) [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05074810"},{"key":"e_1_3_4_39_1","unstructured":"A Phase I\/II study of AMG 510 in combination with MVASI in patients with advanced unresectable or metastatic KRAS G12C mutant NSCLC with asymptomatic brain metastasis [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05180422"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1167"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02752"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212419"},{"key":"e_1_3_4_43_1","unstructured":"A Phase 1\/1b trial of MRTX849 in combination with BI 1701963 in patients with advanced solid tumors with KRAS G12C mutation [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04975256"},{"key":"e_1_3_4_44_1","unstructured":"A Phase 1\/2 trial of MRTX849 in combination with TNO155 in patients with advanced solid tumors with KRAS G12C mutation KRYSTAL 2 [Internet]. 2020. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04330664"},{"key":"e_1_3_4_45_1","unstructured":"A Phase 1\/1b trial of MRTX849 in combination with palbociclib in patients with advanced solid tumors with KRAS G12C mutation [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05178888"},{"key":"e_1_3_4_46_1","unstructured":"A randomized Phase 3 study of MRTX849 versus docetaxel in patients with Previously treated non-small cell lung cancer with KRAS G12C mutation [Internet]. 2020. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04685135"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0158"},{"key":"e_1_3_4_48_1","unstructured":"A Phase Ib\/II Open-label multi-center dose escalation study of JDQ443 in patients with advanced solid tumors harboring the KRAS G12C mutation [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04699188"},{"key":"e_1_3_4_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS9144"},{"key":"e_1_3_4_50_1","unstructured":"KontRASt-03: a Phase Ib\/II multicenter Open-label platform study of JDQ443 with select combinations in patients with advanced solid tumors harboring the KRAS G12C mutation [Internet]. 2022. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05358249"},{"key":"e_1_3_4_51_1","unstructured":"A Phase 1\/2 multi-center Open-label study to evaluate the safety tolerability pharmacokinetics and preliminary evidence of antitumor activity of JAB-21822 monotherapy and combination therapy in adult patients with advanced solid tumors harboring KRAS G12C mutation [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05002270"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyab080"},{"key":"e_1_3_4_53_1","unstructured":"Open-Label A. Multi-center Phase I\/II clinical study evaluating the safety\/Tolerability pharmacokinetics and effectiveness of GFH925 in patients with advanced solid tumors with KRAS G12C mutations [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05005234"},{"key":"e_1_3_4_54_1","unstructured":"Phase I clinical study on the safety tolerance pharmacokinetics and efficacy of YL-15293 in patients with advanced solid tumor with KRAS mutation [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05173805"},{"key":"e_1_3_4_55_1","unstructured":"A Phase 1\/2 study of LY3499446 administered to patients with advanced solid tumors with KRAS G12C mutation [Internet]. 2019. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04165031"},{"key":"e_1_3_4_56_1","volume-title":"Discovery and development of RAS (ON) inhbitors beyond KRASG12C2021: AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021; Virtual meeting.","author":"Kelsey S","unstructured":"Kelsey S, editor. Discovery and development of RAS (ON) inhbitors beyond KRASG12C2021: AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021; Virtual meeting."},{"key":"e_1_3_4_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0840"},{"key":"e_1_3_4_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.70132"},{"key":"e_1_3_4_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-03569-x"},{"key":"e_1_3_4_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917239"},{"key":"e_1_3_4_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105281"},{"key":"e_1_3_4_62_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0365"},{"key":"e_1_3_4_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0142"},{"key":"e_1_3_4_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24604"},{"key":"e_1_3_4_65_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4765"},{"key":"e_1_3_4_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0212-z"},{"key":"e_1_3_4_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-017-0530-5"},{"key":"e_1_3_4_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-020-00714-0"},{"key":"e_1_3_4_69_1","unstructured":"Combination of MEK inhibitor binimetinib and CDK4\/6 inhibitor palbociclib in KRAS and NRAS mutant metastatic colorectal cancers [Internet]. 2019. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03981614"},{"key":"e_1_3_4_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-020-00975-6"},{"key":"e_1_3_4_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.12.002"},{"key":"e_1_3_4_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.05.032"},{"key":"e_1_3_4_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02077-w"},{"key":"e_1_3_4_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09898-0"},{"key":"e_1_3_4_75_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9153"},{"key":"e_1_3_4_76_1","unstructured":"Phase I study of the CDK4\/6 inhibitor palbociclib (PD-0332991) in combination with the MEK inhibitor binimetinib (MEK162) for patients with advanced KRAS mutant non-small cell lung cancer [Internet]. 2017. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03170206"},{"key":"e_1_3_4_77_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c09318"},{"key":"e_1_3_4_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04367-3"},{"key":"e_1_3_4_79_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308795"},{"key":"e_1_3_4_80_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0655"},{"key":"e_1_3_4_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00753-3"},{"key":"e_1_3_4_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_3_4_83_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_3_4_84_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02107"},{"key":"e_1_3_4_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.013"},{"key":"e_1_3_4_86_1","doi-asserted-by":"publisher","DOI":"10.2217\/pme-2021-0128"},{"key":"e_1_3_4_87_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001895"},{"key":"e_1_3_4_88_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf0992"},{"key":"e_1_3_4_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031754"},{"key":"e_1_3_4_90_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609279"},{"key":"e_1_3_4_91_1","unstructured":"A Phase II study using short-term cultured autologous tumor-infiltrating lymphocytes following a lymphodepleting regimen in metastatic cancers plus the administration of pembrolizumab [Internet]. 2010. Available from: https:\/\/clinicaltrials.gov\/study\/NCT01174121"},{"key":"e_1_3_4_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0477-6"},{"key":"e_1_3_4_93_1","unstructured":"A Phase 1\/2 study of GRT-C903\/GRT-R904 a vaccine targeting shared neoantigens in combination with immune checkpoint blockade for patients with advanced solid tumors [Internet]. 2019. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03953235"},{"key":"e_1_3_4_94_1","unstructured":"Pooled mutant KRAS-Targeted long peptide vaccine combined with nivolumab and ipilimumab for patients with resected MMR-p colorectal and pancreatic cancer [Internet]. 2019. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04117087"}],"container-title":["Expert Opinion on Investigational Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.tandfonline.com\/doi\/pdf\/10.1080\/13543784.2025.2611395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:39:55Z","timestamp":1768995595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/13543784.2025.2611395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":92,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,2]]}},"alternative-id":["10.1080\/13543784.2025.2611395"],"URL":"https:\/\/doi.org\/10.1080\/13543784.2025.2611395","relation":{},"ISSN":["1354-3784","1744-7658"],"issn-type":[{"value":"1354-3784","type":"print"},{"value":"1744-7658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ieid20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ieid20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}