Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells

Ciraci P, Studiale V, Taravella A, Antoniotti C, Cremolini C (2025) Late-line options for patients with metastatic colorectal cancer: a review and evidence-based algorithm. Nat Rev Clin Oncol 22:28–45. https://doi.org/10.1038/s41571-024-00965-0

Article  PubMed  Google Scholar 

Knudsen MD, Wang K, Wang L, Polychronidis G, Berstad P, Hjartaker A, Fang Z, Ogino S, Chan AT, Song M (2025) Colorectal cancer incidence and mortality after negative colonoscopy screening results. JAMA Oncol 11:46–54. https://doi.org/10.1001/jamaoncol.2024.5227

Article  PubMed  Google Scholar 

Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J (2024) Cancer incidence and mortality in China, 2022. J Natl Cancer Cent 4:47–53. https://doi.org/10.1016/j.jncc.2024.01.006

Article  PubMed  PubMed Central  Google Scholar 

Luo S, Yue M, Wang D, Lu Y, Wu Q, Jiang J (2024) Breaking the barrier: epigenetic strategies to combat platinum resistance in colorectal cancer. Drug Resist Updat 77:101152. https://doi.org/10.1016/j.drup.2024.101152

Article  CAS  PubMed  Google Scholar 

Wang Q, Ma C, Yang B, Zheng W, Liu X, Jian G (2025) Dysregulation of DNA methylation in colorectal cancer: biomarker, immune regulation, and therapeutic potential. Int Immunopharmacol 145:113766. https://doi.org/10.1016/j.intimp.2024.113766

Article  CAS  PubMed  Google Scholar 

Wang Y, Wang C, Zhong R, Wang L, Sun L (2024) Research progress of DNA methylation in colorectal cancer (Review). Mol Med Rep 30:154. https://doi.org/10.3892/mmr.2024.13278

Article  CAS  PubMed  PubMed Central  Google Scholar 

Singh H, Longo DL, Chabner BA (2015) Improving prospects for targeting RAS. J Clin Oncol 33:3650–3659. https://doi.org/10.1200/JCO.2015.62.1052

Article  CAS  PubMed  Google Scholar 

Riedl JM, Fece F, de la Cruz JJ, Lin C, Parseghian JE, Kim H, Matsubara H, Barnes B, Caughey BL, Norden A, Morales EW, Kushner S, Ehnstrom H, Nakamura PS, Patel H, Ellis L, Pappas A, Vakaris JF, Gainor S, Kopetz SJ, Klempner AR, Parikh AN, Hata RS, Heist, Corcoran RB (2025) Genomic landscape of clinically acquired resistance alterations in patients treated with KRAS(G12C) inhibitors. Ann Oncol. https://doi.org/10.1016/j.annonc.2025.01.020

Article  PubMed  Google Scholar 

Guo Y, Hu C, Cai K, Long G, Cai D, Yu Z, Huang X, Cai Z, Hu P, Chen Y, Gao F, Wu X (2025) KRAS inhibitors may prevent colorectal cancer metachronous metastasis by suppressing TGF–beta mediated epithelial–mesenchymal transition. Mol Med Rep 31:24. https://doi.org/10.3892/mmr.2024.13389

Article  CAS  PubMed  Google Scholar 

Haigis KM (2017) KRAS alleles: the devil is in the detail. Trends Cancer 3:686–697. https://doi.org/10.1016/j.trecan.2017.08.006

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cercek A, Braghiroli MI, Chou JF, Hechtman JF, Kemeny N, Saltz L, Capanu M, Yaeger R (2017) Clinical features and outcomes of patients with colorectal cancers harboring NRAS mutations. Clin Cancer Res 23:4753–4760. https://doi.org/10.1158/1078-0432.CCR-17-0400

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu G, Pei L, Xia H, Tang Q, Bi F (2021) Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer 20:143. https://doi.org/10.1186/s12943-021-01441-4

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang L, Guo Z, Wang F, Fu L (2021) KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther 6:386. https://doi.org/10.1038/s41392-021-00780-4

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA, Burkard MR, Fell JB, Fischer JP, Vigers GP, Xue Y, Gatto S, Fernandez-Banet J, Pavlicek A, Velastagui K, Chao RC, Barton J, Pierobon M, Baldelli E, Patricoin EF, Cassidy DP, Marx MA, Rybkin II, Johnson ML, Ou SI, Lito P, Papadopoulos KP, Janne PA, Olson P, Christensen JG (2020) The KRAS(G12C) inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-Mutant cancers in mouse models and patients. Cancer Discov 10:54–71. https://doi.org/10.1158/2159-8290.CD-19-1167

Article  CAS  PubMed  Google Scholar 

Cox AD, Der CJ (2025) Undruggable KRAS: druggable after all. Genes Dev 39:132–162. https://doi.org/10.1101/gad.352081.124

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo C, Chenard-Poirier M, Roda D, de Miguel M, Harris SJ, Candilejo IM, Sriskandarajah P, Xu W, Scaranti M, Constantinidou A, King J, Parmar M, Turner AJ, Carreira S, Riisnaes R, Finneran L, Hall E, Ishikawa Y, Nakai K, Tunariu N, Basu B, Kaiser M, Lopez JS, Minchom A, de Bono JS, Banerji U (2020) Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study. Lancet Oncol 21:1478–1488. https://doi.org/10.1016/S1470-2045(20)30464-2

Article  CAS  PubMed  Google Scholar 

Han LY, Yu H, Wang S, Bao YR, Li TJ, Zheng Y, Luo X, Jia MN, Zhang Q, Meng XS (2024) Classical prescription floris sophorae powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway. J Ethnopharmacol 325:117805. https://doi.org/10.1016/j.jep.2024.117805

Article  CAS  PubMed  Google Scholar 

Peng ZQ, Fang W, Wu B, He M, Li SH, Wei J, Hao Y, Jin LJ, Liu MQ, Zhang X, Wei YE, Ge YW, Wei YH, Qian HL, Zhang YJ, Jiang JY, Chang ZJ, Rao Y, Zhang XL, Cui CP, Zhang LQ (2025) Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer. Nat Chem Biol 21:59–70. https://doi.org/10.1038/s41589-024-01683-5

Article  CAS  PubMed  Google Scholar 

Xiong H, Li Y, Liu MH (2023) DEPDC1B is involved in the proliferation, metastasis, cell cycle arrest and apoptosis of colon cancer cells by regulating NUP37. Mol Med Rep 27:126 Artn 12610.3892/Mmr.2023.13013

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sorokin AV, Kanikarla Marie P, Bitner L, Syed M, Woods M, Manyam G, Kwong LN, Johnson B, Morris VK, Jones P, Menter DG, Lee MS, Kopetz S (2022) Targeting RAS mutant colorectal cancer with dual inhibition of MEK and CDK4/6. Cancer Res 82:3335–3344. https://doi.org/10.1158/0008-5472.CAN-22-0198

Article  CAS  PubMed  PubMed Central  Google Scholar 

Desai J, Gan H, Barrow C, Jameson M, Atkinson V, Haydon A, Millward M, Begbie S, Brown M, Markman B, Patterson W, Hill A, Horvath L, Nagrial A, Richardson G, Jackson C, Friedlander M, Parente P, Tran B, Wang L, Chen Y, Tang Z, Huang W, Wu J, Zeng D, Luo L, Solomon B (2020) Phase I, open-label, dose-escalation/dose-expansion study of Lifirafenib (BGB-283), an RAF family kinase inhibitor, in patients with solid tumors. J Clin Oncol 38:2140–2150. https://doi.org/10.1200/JCO.19.02654

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dong L, Choi H, Budhu S, Schulze I, Verma S, Mangarin LM, Estrada Nevarro V, Mehanna N, Khan JF, Venkatesh D, Thach D, Rosen N, Wolchok JD, Merghoub T (2024) Intermittent MEK Inhibition with GITR costimulation rescues T-cell function for increased efficacy with CTLA-4 Blockade in solid tumor models. Cancer Immunol Res 12:1392–1408. https://doi.org/10.1158/2326-6066.CIR-23-0729

Article  CAS  PubMed  Google Scholar 

(2021) Dual RAF-MEK inhibitor assessed. Cancer Discov 11:5–6. https://doi.org/10.1158/2159-8290.CD-NB2020-101

Ishii N, Harada N, Joseph EW, Ohara K, Miura T, Sakamoto H, Matsuda Y, Tomii Y, Tachibana-Kondo Y, Iikura H, Aoki T, Shimma N, Arisawa M, Sowa Y, Poulikakos PI, Rosen N, Aoki Y, Sakai T (2013) Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res 73:4050–4060. https://doi.org/10.1158/0008-5472.CAN-12-3937

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hartwich TMP, Mansolf M, Demirkiran C, Greenman M, Bellone S, McNamara B, Nandi SP, Alexandrov LB, Yang-Hartwich Y, Coma S, Pachter J, Santin AD (2024) Preclinical evaluation of Avutometinib and Defactinib in high-grade endometrioid endometrial cancer. Cancer Med 13:e70210. https://doi.org/10.1002/cam4.70210

Article  CAS  PubMed  PubMed Central 

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