Santos E, Martin-Zanca D, Reddy EP, Pierotti MA, Della Porta G, Barbacid M. Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science. 1984;223(4637):661–4. https://doi.org/10.1126/science.6695174.

Article  CAS  PubMed  Google Scholar 

Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170(1):17–33. https://doi.org/10.1016/j.cell.2017.06.009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cook JH, Melloni GEM, Gulhan DC, Park PJ, Haigis KM. The origins and genetic interactions of KRAS mutations are allele- and tissue-specific. Nat Commun. 2021;12(1):1808. https://doi.org/10.1038/s41467-021-22125-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim HJ, Lee HN, Jeong MS, Jang SB. Oncogenic KRAS: signaling and drug resistance. Cancers (Basel). 2021. https://doi.org/10.3390/cancers13225599.

Article  PubMed  PubMed Central  Google Scholar 

Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021;6(1):386. https://doi.org/10.1038/s41392-021-00780-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu Z, Golay HG, Barbie DA. Targeting pathways downstream of KRAS in lung adenocarcinoma. Pharmacogenomics. 2014;15(11):1507–18. https://doi.org/10.2217/pgs.14.108.

Article  CAS  PubMed  Google Scholar 

Byun JK, Park M, Yun JW, et al. Oncogenic KRAS signaling activates mTORC1 through COUP-TFII-mediated lactate production. EMBO Rep. 2019. https://doi.org/10.15252/embr.201847451.

Article  PubMed  PubMed Central  Google Scholar 

Gao Z, Chen J-F, Li X-G, et al. KRAS acting through ERK signaling stabilizes PD-L1 via inhibiting autophagy pathway in intrahepatic cholangiocarcinoma. Cancer Cell Int. 2022;22(1):128. https://doi.org/10.1186/s12935-022-02550-w.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Waters AM, Der CJ. KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb Perspect Med. 2018. https://doi.org/10.1101/cshperspect.a031435.

Article  PubMed  PubMed Central  Google Scholar 

El Osta B, Behera M, Kim S, et al. Characteristics and outcomes of patients with metastatic KRAS-mutant lung adenocarcinomas: the lung cancer mutation consortium experience. J Thorac Oncol. 2019;14(5):876–89. https://doi.org/10.1016/j.jtho.2019.01.020.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jia Y, Jiang T, Li X, et al. Characterization of distinct types of Kras mutation and its impact on first line platinum based chemotherapy in Chinese patients with advanced non small cell lung cancer. Oncol Lett. 2017;14(6):6525–32. https://doi.org/10.3892/ol.2017.7016.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nadal E, Chen G, Prensner JR, et al. KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. J Thorac Oncol. 2014;9(10):1513–22. https://doi.org/10.1097/JTO.0000000000000305.

Article  CAS  PubMed  Google Scholar 

Liu J, Kang R, Tang D. The KRAS-G12C inhibitor: activity and resistance. Cancer Gene Ther. 2022;29(7):875–8. https://doi.org/10.1038/s41417-021-00383-9.

Article  CAS  PubMed  Google Scholar 

Pantsar T. The current understanding of KRAS protein structure and dynamics. Comput Struct Biotechnol J. 2020;18:189–98. https://doi.org/10.1016/j.csbj.2019.12.004.

Article  CAS  PubMed  Google Scholar 

Xu K, Park D, Magis AT, et al. Small molecule KRAS agonist for mutant KRAS cancer therapy. Mol Cancer. 2019;18(1):85. https://doi.org/10.1186/s12943-019-1012-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xue JY, Zhao Y, Aronowitz J, et al. Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition. Nature. 2020;577(7790):421–5. https://doi.org/10.1038/s41586-019-1884-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang J, Park D, Shin DM, Deng X. Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities. Acta Biochim Biophys Sin (Shanghai). 2016;48(1):11–6. https://doi.org/10.1093/abbs/gmv118.

Article  CAS  PubMed  Google Scholar 

Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov. 2014;13(11):828–51. https://doi.org/10.1038/nrd4389.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Molinier O, Goupil F, Debieuvre D, et al. Five-year survival and prognostic factors according to histology in 6101 non-small-cell lung cancer patients. Respir Med Res. 2020;77:46–54. https://doi.org/10.1016/j.resmer.2019.10.001.

Article  CAS  PubMed  Google Scholar 

Dogan S, Shen R, Ang DC, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18(22):6169–77. https://doi.org/10.1158/1078-0432.ccr-11-3265.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ostrem JM, Shokat KM. Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design. Nat Rev Drug Discov. 2016;15(11):771–85. https://doi.org/10.1038/nrd.2016.139.

Article  CAS  PubMed  Google Scholar 

Gorfe AA, Grant BJ, McCammon JA. Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins. Structure. 2008;16(6):885–96. https://doi.org/10.1016/j.str.2008.03.009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagasaka M, Potugari B, Nguyen A, Sukari A, Azmi AS, Ou SI. KRAS Inhibitors- yes but what next? Direct targeting of KRAS- vaccines, adoptive T cell therapy and beyond. Cancer Treat Rev. 2021;101: 102309. https://doi.org/10.1016/j.ctrv.2021.102309.

Article  CAS  PubMed  Google Scholar 

Reck M, Carbone DP, Garassino M, Barlesi F. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann Oncol. 2021;32(9):1101–10. https://doi.org/10.1016/j.annonc.2021.06.001.

Article  CAS  PubMed  Google Scholar 

Hallin J, Engstrom LD, Hargis L, et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of kras-mutant cancers in mouse models and patients. Cancer Discov. 2020;10(1):54–71. https://doi.org/10.1158/2159-8290.CD-19-1167.

Article  CAS  PubMed  Google Scholar 

Jarvis LM. Have drug hunters finally cracked KRas? 2016. https://cen.acs.org/articles/94/i23/drug-hunters-finally-cracked-KRas.html#:~:text=Fesik%20pioneered%20the%20NMR%2Dbased,down%20KRas%2C%20UCSF's%20McCormick%20notes. Accessed 18 Feb 2023.

Do K, Speranza G, Bishop R, et al. Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244, ARRY-142886) in patients with colorectal cancer. Invest New Drugs. 2015;33(3):720–8. https://doi.org/10.1007/s10637-015-0212-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jänne PA, van den Heuvel MM, Barlesi F, et al. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non-small cell lung cancer: the SELECT-1 randomized clinical trial. JAMA. 2017;317(18):1844–53. https://doi.org/10.1001/jama.2017.3438.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Proietti I, Skroza N, Michelini S, et al. BRAF inhibitors: molecular targeting and immunomodulatory actions. Cancers (Basel). 2020. https://doi.org/10.3390/cancers12071823.

Article  PubMed  Google Scholar 

King AJ, Arnone MR, Bleam MR, et al. Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS ONE. 2013;8(7): e67583. https://doi.org/10.1371/journal.pone.0067583.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gentilcore G, Madonna G, Mozzillo N, et al. Effect of dabrafenib on melanoma cell lines harbouring the BRAF(V600D/R) mutations. BMC Cancer. 2013;13:17. https://doi.org/10.1186/1471-2407-13-17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Buhrman G, O’Connor C, Zerbe B, et al. Analysis of binding site hot spots on the surface of Ras GTPase. J Mol Biol. 2011;413(4):773–89. https://doi.org/10.1016/j.jmb.2011.09.011.

Article  CAS  PubMed  PubMed Central