Colorectal carcinoma (CRC) represents the third most common cancer worldwide. Approximately 20% of patients present with metastatic disease at diagnosis, and 30–50% experience disease recurrence over time. For metastatic CRC (mCRC), the standard treatment consists of chemotherapy combined with a targeted agent based on molecular profile, such as RAS, BRAF, and MSI status. Anti-angiogenic drugs, which inhibit the formation of new blood vessels, have an established role in the management of mCRC. Mounting evidence highlights the critical interplay among angiogenesis, hypoxia, and the immune response in tumor progression. These insights have paved the way for testing novel combinations and molecules to control cancer progression. In particular, combining anti-angiogenic agents with immune checkpoint inhibitors has shown promise in improving outcomes for mCRC patients. Among emerging therapies, the novel anti-angiogenic agent fruquintinib has recently demonstrated clinical efficacy in the treatment of mCRC. Based on the data discussed in the present narrative review, the therapeutic landscape of mCRC appears poised for significant evolution in the near future. While numerous challenges and unanswered questions remain, the emergence of innovative therapeutic combinations and agents provides a promising opportunity for improving patient outcomes in mCRC.
Nardo et al. (2025) studied this question.