Resistance management of sunitinib

Sunitinib is a VEGFR tyrosine kinase inhibitor that has been approved as a first-line treatment for patients with advanced renal cell carcinoma (RCC) for more than a decade. However, patients treated with sunitinib gradually develop resistance to the drug. Recently, immune checkpoint inhibitors (ICIs) have been approved as second-line treatments for patients with RCC who are resistant to anti-angiogenic therapy. However, how the development of resistance to anti-angiogenic inhibitors affects the efficacy of ICIs remains unknown.

Established 2 sunitinib-resistant renal cell carcinoma cell lines. Characterization of these cell lines demonstrated in vitro acquired resistance to sunitinib via viability assays. Compared with the parental cell line, sunitinib-resistant RCC cell lines exhibit abnormal overexpression of Axl and PDL1, as well as reduced activation of the STAT3 pathway and LDHA. Metabolomic and transcriptomic analyzes after in vitro treatment of sunitinib-resistant RCC cells with ICIs revealed that ICIs induced metabolic reorganization of RCC cell lines characterized by enhanced OXPHOS and glutamine metabolism. This metabolic reorganization of sunitinib-resistant RCC cells after ICI treatment is consistent with that observed in tumors from patients who benefit from ICI treatment. These data suggest that sunitinib resistance may support the efficacy of ICIs in advanced renal cancer.

The original sunitinib drug has been launched in China and has entered the scope of Class B medical insurance. SpecificationsThe price of 12.5mg*28 tablets is around RMB 3,500. The original sunitinib drug has also been launched overseas. The price of 12.5mg*7 tablets is around RMB 1,500 (the price may fluctuate due to the exchange rate). There are also generic drugs produced in other countries. The price of 12.5mg*28 tablets produced by an Indian pharmaceutical factory is around RMB 750 (the price may fluctuate due to the exchange rate). The generic drugs produced abroad are basically the same as the original drugs at home and abroad. There may be differences in the prices of different specifications of drugs.