Resistance of renal cell carcinoma to targeted therapy

Abstract

Targeted therapy has replaced immunotherapy as the standard of care for metastatic renal cell carcinoma (RCC). Currently available targeted agents include multi- tyrosine kinase inhibitors (axitinib, sunitinib, sorafenib and pazopanib), mammalian target of rapamycin (mTOR) kinase inhibitors (temsirolimus and everolimus) and bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF). Despite the beneficial clinical outcomes, resistance to therapy is emerging as a new challenge. Resistance to therapy can be either intrinsic or extrinsic (acquired). About 30% of patients have intrinsic resistant and almost all patients who respond initially will develop acquired resistance within 12 months of treatment. In this chapter, we summarize the current challenges of drug resistance in the effective treatment of metastatic RCC with particular emphasis on targeted therapies