期刊
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
卷 13, 期 10, 页码 1288-1301出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4251/wjgo.v13.i10.1288
关键词
Colorectal cancer; Anti-epidermal growth factor receptor therapy; KRAS; NRAS; BRAF; HER2; Microsatellite instability; MUTYH; Hereditary cancer
资金
- Ministry of Science and Higher Education of the Russian Federation [075-15-2020-789]
Molecular genetic analysis plays a crucial role in colorectal cancer management, guiding treatment choices such as targeted therapies and immune checkpoint inhibitors. The emerging technologies of liquid biopsy and next-generation sequencing are revolutionizing the landscape of CRC molecular diagnosis.
Molecular genetic analysis is an integral part of colorectal cancer (CRC) management. The choice of systemic therapy for CRC is largely based on the results of tumor molecular testing. Evaluation of the KRAS and NRAS gene status is mandatory for consideration of anti-epidermal growth factor receptor (EGFR) therapy. Tumors with the BRAF V600E substitution are characterized by aggressive behaviour, may require intensified cytotoxic regimens and benefit from combined BRAF and EGFR inhibition. The inactivation of DNA mismatch repair (MMR), or MUTYH gene, or DNA polymerase epsilon results in excessive tumor mutational burden; these CRCs are highly antigenic and therefore sensitive to immune checkpoint inhibitors. Some CRCs are characterized by overexpression of the HER2 oncogene and respond to the appropriate targeted therapy. There are CRCs with clinical signs of hereditary predisposition to this disease, which require germline genetic testing. Liquid biopsy is an emerging technology that has the potential to assist CRC screening, control the efficacy of surgical intervention and guide disease monitoring. The landscape of CRC molecular diagnosis is currently undergoing profound changes due to the increasing use of next generation sequencing.
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