Tyrosine kinase inhibitors and anti-angiogenic therapies in kidney cancer.

Renal cell carcinoma (RCC) is a heterogeneous disease as reflected in its presentation and clinical course, pathological subtypes, nuclear grades and molecular biology. Emerging data indicate that renal tumors express a variety of molecular tumor markers and unique patterns of gene expression. Clinically the disease behaves quite heterogeneously, with courses ranging from indolent to highly aggressive. Surgical monotherapy or as part of a multimodal approach remains the standard of care for most cases of RCC. Radical or partial nephrectomy is associated with a 5-year cancer specific survival (CSS) of 85-97% for pT1 tumors. Unfortunately, 20% of patients have either locally advanced or node positive (N+) RCC while another 22% have metastatic RCC (mRCC) at presentation. Unlike the outcomes in early localized disease, survival rates for N+ patients are poor and patients with mRCC are rarely cured despite aggressive multimodal therapy. Classic cytotoxic chemotherapy has repeatedly been shown to have little effect and only 5-20% of patients with mRCC respond to immunologic agents such as interferon and/or interleukin. Cytoreductive nephrectomy with systemic immunotherapy is associated with few cures with median survivals of 12-24 months. Recent advances in our understanding of the molecular origins and pathways of RCC have led to the development of more effective targeted therapies. Here we review the molecular pathways that define the pertinent therapeutic targets in RCC and the clinical data for these new and promising agents.