Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.

Renal cell carcinoma (RCC) is a highly vascularized and metastatic malignancy of the kidney. The 5-year overall survival rate of RCC patients remains poor despite the development of therapeutic modalities. Therefore, identifying novel approaches to increase the sensitivity of RCC cells to drugs could help prolong patient survival. Recently, Drug repurposing, which leverages the established safety profiles and pharmacological properties of existing medications, has emerged as a promising alternative to traditional drug development. This approach can accelerate the translation of new therapies into clinical practice and is often associated with lower attrition rates in clinical trials. Recent evidence supports the therapeutic potential of various repurposed drugs against RCC. This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance.