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Pathobiology, Prognosis, and Targeted Therapy for Renal Cell Carcinoma

Exploiting the Hypoxia-Induced Pathway

Departments of Urology (A. J. P., G. Z., A. S. B.) and Medicine (R. A. F.), David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095

Historically, clinical factors have been used as prognostic markers for patients with renal cell carcinoma (RCC). Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of RCC have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for RCC patients. This report reviews the molecular mechanisms of the hypoxia-induced pathway that play an essential role in angiogenesis, glycolysis, and apoptosis of common cancers and may be responsible for the ability of the cancers to adapt to a hypoxic environment and also for their resistance to radiation and chemotherapy. The hypoxia-induced pathway has been linked genetically to RCC through the von Hippel-Lindau tumor suppressor gene, which is inactivated in a majority of clear cell RCCs. Therefore, RCC is a particularly attractive clinical model to exploit the hypoxia-induced pathway for new therapeutic interventions. von Hippel-Lindau, hypoxia inducible factor 1, carbonic anhydrase IX, vascular endothelial growth factor, and other important members of the hypoxia-induced gene family, provide new molecular targets for diagnosis, prognosis, and immunotherapy of RCC.

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