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Abstract
The selection of minor mutations in KRAS gene suggested for analysis in colorectal cancer patients before anti-EGFR treatment are discussed in line with the available clinical data.
It is shown that to date there are no unambiguous results of clinical studies that would demonstrate the clinical significance of all known mutations in codons 59, 61, 117, 146 of the KRAS gene in colorectal cancer. Only those KRAS mutations the analysis of which is fully justified based on clinical data suggested to be included in the list of mutations recommended for the analysis in clinics. In conclusion, it is noted that the analysis of mutations before the use of anti-EGFR therapy does not have statistically significant clinical justification for mutations A146V, A146P and is not justified for all mutations in codon 59 of KRAS gene.
References
Lièvre A., Bachet J., Le Corre D. et al. KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer. Cancer Res. American Association for Cancer Research. 2006; 66(8):3992–3995.-DOI: 10.1158/0008-5472.CAN-06-0191.
Allegra C.J., Rumble R.B., Hamilton S.R. et al. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American society of clinical oncology provisional clinical opinion update 2015. Journal of Clinical Oncology. American Society of Clinical Oncology. 2016; 34(2):179–185.-DOI: 10.1200/JCO.2015.63.9674.
Bokemeyer C., Köhne C.-H., Ciardiello F. et al. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer. Pergamon. 2015; 51(10):1243–1252.-DOI: 10.1016/j.ejca.2015.04.007.
COSMIC / Catalogue of Somatic Mutations in Cancer [Electronic resource]. URL: https://cancer.sanger.ac.uk/cosmic (accessed: 17.09.2024).
Cervantes A., Adam R., Roselló S. et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. Elsevier Ltd. 2023; 34(1):10–32.-DOI: 10.1016/j.annonc.2022.10.003.
Douillard J.-Y., Oliner K.S., Siena S. et al. Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer. New England Journal of Medicine (NEJM/MMS). 2013; 369(11):1023–1034.-DOI: 10.1056/NEJMoa1305275.
De Roock W., De Vriendt V., Normanno N. et al. KRAS, BRAF, PIK3CA, and PTEN mutations: Implications for targeted therapies in metastatic colorectal cancer. The Lancet Oncology. Elsevier. 2011; 12(6):594–603.-DOI: 10.1016/S1470-2045(10)70209-6.
Wójcik P., Kulig J., Okoń K. et al. KRAS mutation profile in colorectal carcinoma and novel mutation--internal tandem duplication in KRAS.. Pol J Pathol. 2008; 59(2):93–96.- PMID: 18669174.
Yuen S.T., Davies H., Chan T.L. et al. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia.. Cancer Research. 2002; 62(22):6451–6455.- URL: https://aacrjournals.org/cancerres/article/62/22/6451/509508/Similarity-of-the-Phenotypic-Patterns-Associated.
Cook J. H., Melloni G. E., Gulhan D. C. et al. The origins and genetic interactions of KRAS mutations are allele- and tissue-specific. Nature Communications. 2021; 12(1):1808.-DOI: 10.1038/s41467-021-22125-z.
Home - My Cancer Genome [Electronic resource]. URL: https://www.mycancergenome.org/ (accessed: 17.09.2024).
Ciardiello F., Lenz H. J., Kohne C. H. et al. Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with/without cetuximab.. https://doi.org/10.1200/jco.2014.32.15_suppl.3506. JCO. 2014; 32:3506–3506.-DOI: 10.1200/jco.2014.32.15_suppl.3506.
M.J. Sorich, M.D. Wiese, A. Rowland et al. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Annals of Oncology. Elsevier. 2015; 26(1):13–21.-DOI: 10.1093/annonc/mdu378.
Loupakis F., Ruzzo A., Cremolini C. et al. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. British Journal of Cancer. 2009; 101: 715–721.-DOI: 10.1038/sj.bjc.6605177.
KRAS | OncoKBTM [Electronic resource]. URL: https://www.oncokb.org/gene/KRAS (accessed: 16.09.2024).
KRAS[gene] - ClinVar - NCBI [Electronic resource]. URL: https://www.ncbi.nlm.nih.gov/clinvar (accessed: 26.09.2024).
Кит О.И., Тимошкина Н.Н., Гвалдин Д.Ю et al. Клинические случаи метастатического колоректального рака, ассоциированные с мутациями A146V, A59G гена KRAS. Сеченовский вестник. 2023; 14(2): 49–56.-DOI: 10.47093/2218-7332.2023.14.2.49-5. [Kit O.I., Timoshkina N.N., Gvaldin D.Y. et al. Case report of metastatic colorectal cancer associated with KRAS A146V and A59G mutations. Sechenov Medical Journal. I.M. Sechenov First Moscow State Medical University. 2023; 14(2):49–56.-DOI: 10.47093/2218-7332.2023.14.2.49-5 (in Rus)].
KRAS | EOD Data SEER*RSA [Electronic resource]. URL: https://staging.seer.cancer.gov/eod_public/input/3.1/colon_rectum/kras/?breadcrumbs=(~view_schema~,~colon_rectum~) (accessed: 16.09.2024).
KRASP - Overview: KRAS Somatic Mutation Analysis, Tumor [Electronic resource]. URL: https://www.mayocliniclabs.com/test-catalog/overview/610679#Clinical-and-Interpretive (accessed: 16.09.2024).
Федянин М. Ю., Гладков О. А., Гордеев С. С. et al. Практические рекомендации по лекарственному лечению рака ободочной кишки, ректосигмоидного соединения и прямой кишки. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2023; 13(3s2):425-482.-DOI: 10.18027/2224-5057-2023-13-3s2-1-425-482. [Fedyanin M. Y., Gladkov O. A., Gordeev S. S. et al. Practical recommendations for drug treatment of cancer of the colon, rectosigmoid junction and rectum. Practical recommendations RUSSCO, part 1. Malignant tumors. 2023; 13(3s2):425-482.-DOI: 10.18027/2224-5057-2023-13-3s2-1-425-482 (in Rus)].
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