Neuropilin-2 (NRP2) mediates sorafenib resistance in clear cell renal cell carcinoma via the NRP2/NF-κB/TNFα axis.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer and is characterized by high aggressiveness and a propensity for metastasis. Although the targeted therapeutic drug sorafenib has achieved significant progress in the treatment of ccRCC, drug resistance remains a major challenge. We found that NRP2 is significantly upregulated in sorafenib-resistant ccRCC cells and is highly expressed in ccRCC tissues, where it promotes cell proliferation, migration, and invasion. These effects are mediated through the NRP2/NF-κB/TNFα axis, which also underlies NRP2-induced sorafenib resistance. Targeting this axis with the TNF-α inhibitor adalimumab effectively reversed sorafenib resistance in ccRCC, suggesting a promising therapeutic strategy.