Redox-sensitive signaling pathways in renal cell carcinoma

Renal cell carcinoma (RCC) is one of the most lethal urological cancers, highly resistant to chemo and radiotherapy. Obesity and smoking are the best-known risk factors of RCC, both related to oxidative stress presence, suggesting a significant role in RCC development and maintenance. Surgical resection is the treatment of choice for localized RCC; however, this neoplasia is hardly diagnosable at its initial stages, occurring commonly in late phases and even when metastasis is already present. Systemic therapies are the option against RCC in these more advanced stages, such as cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies; nevertheless, these strategies are still insufficient. A field poorly analyzed in this neoplasia is the status of cell signaling pathways sensible to the redox state, which have been associated with the development and maintenance of RCC. This review focuses on alterations reported in the following redox-sensitive molecules and signaling pathways in RCC: mitogen-activated protein kinases, protein kinase B (AKT)/tuberous sclerosis complex 2/mammalian target of rapamycin C1, AKT/glycogen synthase kinase 3/β-catenin, nuclear factor κB/inhibitor of κB/epidermal growth factor receptor, and protein kinase Cζ/cut-like homeodomain protein/factor inhibiting hypoxia-inducible factor (HIF)/HIF as potential targets for redox therapy.