Systemic therapy for metastatic colorectal cancer

Systemic therapy for metastatic colorectal cancer. The article provides a 
comprehensive overview of current approaches to treating metastatic colorectal cancer 
(mCRC), with a focus on the biological heterogeneity of the disease and a personalized 
therapy strategy. The key prognostic and predictive factors that determine treatment 
tactics are examined: the location of the primary tumor, the molecular-genetic status 
(RAS/BRAF mutations, MSI-H/dMMR, HER2), as well as the pattern of metastasis (liver, 
lungs, peritoneum). The data from large randomized studies that justify the choice 
between anti-EGFR and anti-VEGF drugs in the first line, depending on the side of 
the lesion, as well as the role of immunotherapy for MSI-H/dMMR tumors, have been 
analyzed in detail. The issues of surgical conversion in borderline resectable metastases, as well as the role of peritoneal and maintenance therapy, are considered separately. The final part systematizes the options for subsequent lines of treatment, including refractory status, with a critical assessment of the efficacy and toxicity profile of trifluridine/tipiracil in combination with bevacizumab, fruquintinib, and regorafenib. Special attention is paid to the 
latest data from clinical trials conducted in 2025–2026, which define future therapeutic directions.