Over the past 20 years, tremendous progress has been made in the treatment of rectal cancer, with significant improvements in survival time. However, palliative chemotherapy remains the main treatment modality for patients with advanced CRC. The drugs used to treat advanced CRC mainly include cytotoxic drugs (fluorouracil-based, oxaliplatin, irinotecan) and targeted drugs, mainly anti-angiogenic drugs (bevacizumab, abciximab, regorafenib) and anti-epidermal growth factor (EGFR) monoclonal antibodies (cetuximab and panitumumab – in patients with wild-type CRC with RAS gene). I. Anti-angiogenic drugs 1. Bevacizumab Bevacizumab, also known as Anvitin, is a recombinant humanized monoclonal antibody IgG1. mainly by binding to circulating human vascular endothelial growth factor (VEGF-A) and blocking its bioactive binding, and can enhance chemotherapeutic drug activity. The results of several studies have shown that its combination with first-line chemotherapy can improve the efficiency and prolong the survival time of patients with advanced CRC to varying degrees. Moreover, Avastin can be continued after disease progression and still provide a survival benefit to patients. Side effects include hypertension, proteinuria, arterial embolism, mucosal bleeding, gastrointestinal perforation, and delayed wound healing, and should be closely monitored. It is worth noting that Avastin does not increase chemotherapy-related toxicity. 2, Abciximab Abciximab is a recombinant human fusion protein that binds tightly to circulating VEGF so that it cannot interact with cell surface receptors. it mainly inhibits VEGF type A and B and placental growth factor, and has a broader mechanism of action than currently available anti-angiogenic drugs such as bevacizumab. in 2012, the US FDA approved its combination with the traditional FOLFIRI regimen (irinotecan, calcium folinate, 5-fluorouracil) in the second line for patients with disease progression on oxaliplatin-containing regimens, regardless of prior treatment with Avastin. Abciximab has similar toxicity to Avastin, but increases chemotherapy-related toxicity. It is not yet approved in China. 3. regorafenib Regorafenib is an oral multi-kinase inhibitor. In preclinical studies, regorafenib was able to inhibit several pro-angiogenic VEGF receptor tyrosine kinases, which play an important role in tumor angiogenesis. The drug also inhibits multiple kinases in the cancer and tumor microenvironment, including VEGFR 1-3, KIT, RET, PDGFR, and FGFR. recent studies have shown that regorafenib significantly improves overall survival in patients with metastatic CRC whose tumors are still progressive after standard therapy. Its toxic side effects include skin reactions on hands and feet, hypertension, fatigue, hyperbilirubinemia, and elevated liver enzyme levels. It is primarily indicated for use in patients with good physical status and adequate organ function. It has been approved for the treatment of metastatic CRC in more than 50 countries worldwide, but has not yet been approved in China. Anti-EGFR monoclonal antibody 1. Cetuximab Cetuximab is a human-mouse chimeric IgG1 monoclonal antibody, which specifically binds to EGF receptors on the surface of multiple cancer cells and competitively blocks EGF and other ligands, blocking intracellular signal transduction pathways through the inhibition of tyrosine kinase (TK) bound to EGF receptors, thereby inhibiting the proliferation of cancer cells and inducing apoptosis of cancer cells. Cetuximab in combination with chemotherapy provides a survival benefit in both first-line, and second-line therapy, and, in patients who fail chemotherapy, cetuximab is able to prolong survival compared to best supportive care. The main side effects include: seat sore-like rash (allergic reaction), hypomagnesemia, etc. 2, panitumumab panitumumab is the first fully humanized IgG2 monoclonal antibody, the mechanism of action and cetuximab the same. Treatment options for RAS wild-type metastatic colorectal cancer include panitumumab combined with FOLFIRI or FOLFOX as first-line or second-line treatment, and panitumumab alone can also be used as third-line treatment options and above. The side effects are essentially the same as those of cetuximab, which is not yet approved in China. In addition to the above targeted drugs, there are several new targeted drugs in clinical trials, and it is believed that in the near future, more and more targeted drugs will be used for the treatment of advanced CRC, bringing more clinical benefits to patients.