Renal cell carcinoma (RCC) is a tumor that is not sensitive to radiation, and radiotherapy alone cannot achieve good results. Chemotherapy has limited effect and low efficiency. Immunotherapy has been used for decades and has proven its efficacy. In recent years, targeted therapeutic drugs have continued to emerge and have become one of the main treatment modalities for advanced kidney cancer. I. Chemotherapy: The application of chemotherapy in RCC has been limited due to its inexact efficacy and obvious adverse effects. As early as the 1980s, several clinical studies have confirmed that RCC is a chemotherapy primary resistant tumor. An MDR-associated glycoprotein expressed on the surface of kidney cancer cells is an important factor contributing to the drug resistance outcome. mdr1, encodes a 170 KD membrane glycoprotein (P-glycoprotein) that acts as an efflux pump and reduces intracellular drug concentrations. Although some compounds were later designed to inhibit the glycoprotein, such as toremifene, verapamil, nifedipine, and cyclosporine A, these approaches did not improve the response rate of drugs such as vincristine. Therefore it has also been suggested that there may be other mechanisms of drug resistance in RCC. The main chemotherapeutic agents still used to treat metastatic RCC (mRCC) are gemcitabine, fluorouracil or capecitabine, and cisplatin. Gemcitabine in combination with fluorouracil or capecitabine is mainly used for renal clear cell carcinoma, while gemcitabine in combination with cisplatin is mainly used for non-clear cell carcinoma-based RCC. doxorubicin can be combined with chemotherapy regimens if the tumor tissue contains sarcoma-like components. However, overall, the effectiveness of chemotherapy for mRCC is low, about 10-15%. Chemotherapy in combination with IFN-a or IL-2 has also not shown an advantage. Immunotherapy has been used in RCC for more than 30 years, and the results show that it does have efficacy, but the efficacy is limited. Interferon-α (IFN-α) is a member of a family of pleiotropic proteins with functions in antiviral, immunomodulatory and antiproliferative activities associated with the regulation of gene expression in specific cell populations. Interleukin-2 (IL-2) is a T-cell regulator that produces IL-2 when T-lymphocytes are activated.IL-2 exerts its biological effects upon binding to receptors and subsequently undergoes clonal proliferation of cytotoxic T-lymphocytes. In the 1990s, IFN-α or IL-2 has been used as a first-line treatment option for mRCC, with an objective response rate of about 13-15%. IL-2 IL-2 is an important immunotherapeutic agent. the overall effectiveness of IL-2 alone in RCC is 15%. High-dose IL-2 is preferred over low-dose therapy. The National Cancer Institute (NCCN) recommends the following IL-2 regimen: High-dose IL-2 regimen: IL-2 (6.0-7.2) x 105 IU/[kg (body weight).8h] given intravenously over 15 minutes on days 1 to 5 and repeated at 9-day intervals on days 15 to 19. Low-dose IL-2 regimen 1: IL-2 2.5×105IU/kg (body weight), IH 5d/w x 1 week, IL-2 1.25×105IU/kg (body weight), IH 5d/w x 6 weeks, every 8 weeks. Low-dose IL-2 regimen 2: IL-2 18MIU/d , IH 5d/w×5-8 weeks Adverse effects: mainly mild to moderate reactions of multi-system grade 1-2, including fatigue (100%), fever (82.9%), subcutaneous nodules at the injection site (68.3%), rash/desquamation (43.9%), diarrhea (24.4%), vomiting (17.1%), elevated transaminases (39%) , elevated blood creatinine (39%), elevated urea nitrogen (22%), anemia (12.2%), dyspnea (12.2%), etc. Most of the adverse effects were reversible. The results of the study suggest that IL-2 treatment at dose levels of 9-18 MIIU is effective in Chinese patients with metastatic kidney cancer and the adverse effects are mild. Recommended dose of IL-2 for Chinese patients: 18MIU IH 5d/w x 1 week, 9MIU q12h d1-2, 9MIU qd d3-5 x 3 weeks, repeated after 1 week of rest. IFN-α IFN-α was the first genetically recombinant cytokine used clinically and has been reported in the literature for the treatment of metastatic renal cancer since 1983. Recommended therapeutic dose of IFN-α: 9 MIU per dose, im or IH, 3 times/week for 12 weeks. It can be gradually increased from 3MIU per dose, 3MIU per dose in the first week, 6MIU per dose in the second week, and 9MIU per dose in the third week. The main adverse effects include (1) serum sickness-like reactions: fever, malaise, muscle pain, arthralgia, etc. (60%-90%); (2) leukopenia (40%); (3) thrombocytopenia (25%-55%); (4) increased transaminases (15%-25%), etc. 15%-25%), etc. If patients cannot tolerate 9MIU per dose, the dose can be reduced to 6MIU per dose or even 3MIU per dose. Molecular targeted therapy The VHL gene has been successfully cloned and its encoded protein function has been elucidated, and high frequency mutations or episodic silencing of the gene in disseminated clear cell carcinoma have also been recognized. These are the basis of studies using the VEGF and PDGF pathways as molecularly targeted therapies. These growth factors bind to tyrosine kinase receptors to regulate cell proliferation and survival and can promote tumor-associated angiogenesis and growth. Therefore, inhibition of VEGF and PDGF signaling pathways may therefore prevent angiogenesis and tumor progression. The US Food and Drug Administration (FDA) has approved six targeted therapeutic agents for the treatment of advanced kidney cancer, namely the small molecule multikinase inhibitors sorafenib, sunitinib and pazopanib, the vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in combination with interferon, and the mTOR inhibitors tesilomox and everolimus. The EAU recommends first-line treatment for advanced kidney cancer as follows: sunitinib, pazopanib, bevacizumab combined with interferon. The NCCN recommends the following drugs for the first-line treatment of advanced kidney cancer: sorafenib, sunitinib and pazopanib, the monoclonal antibody to vascular endothelial growth factor (VEGF) bevacizumab combined with interferon, and the mTOR inhibitor tesilomox. The main drugs used in China are sorafenib and sunitinib. sorafenib is an oral tyrosine kinase inhibitor. ratain MG et al. enrolled 202 cases of advanced renal cell carcinoma and received sorafenib 400 mg bid po. after 12 weeks, 73 cases had tumor shrinkage of more than 25% and 65 cases had stable disease. Stable patients were followed by 12 weeks of clinical observation with randomized groups of sorafenib or placebo. 32 of them continued to receive sorafenib and 33 received placebo for a total of 24 weeks. The results showed that at week 24, 50% of the patients in the sorafenib group had progression-free disease compared to 18% in the placebo group (p = 0.0077). Progression-free survival was 24 weeks in the sorafenib-treated group and 6 weeks in the placebo group (P = 0.0087). Escudier B et al. conducted a randomized controlled phase III clinical trial of sorafenib versus placebo. A total of 905 cases of advanced renal clear cell carcinoma were enrolled in the study, and subjects were randomized 1:1. The interim progression-free survival was 24 weeks in the sorafenib group versus 12 weeks in the placebo group (P = 0.000001). A study analyzing the efficacy and safety of sorafenib for patients with advanced renal cell carcinoma was also conducted in China. Their disease control rates were generally consistent with those reported abroad. Sunitinib Sunitinib (sunitinib) is also an oral tyrosine kinase inhibitor. 750 patients with metastatic renal cancer diagnosed as clear cell carcinoma were enrolled in a clinical phase III trial by Motzer et al. and randomized 1:1 to the sunitinib group (sunitinib 50 mg po qd) and the IFN-α group. The results showed an ORR of 31% in the sunitinib group compared with 6% in the IFN-α group (P=0.000001). The median progression-free survival PFS was 11 months in the former and 5 months in the latter (P=0.00001). The main side effects in the sunitinib group were hypertension, dermatitis, and stomatitis.