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Renal Cell Carcinoma pp 237–252Cite as

Anti-VEGF and VEGFR Monoclonal Antibodies in RCC

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Abstract

Renal cell carcinoma accounts for 2–3 % of all malignant diseases in adults. It is the seventh most common cancer in men and the ninth most common in women [1]. Its management has undergone a transformation in the past few years: novel targeted therapies have expanded considerably for patients with metastatic renal cell carcinoma (mRCC). Previously, systemic treatment was limited to cytokine therapy with interleukin (IL)-2 or interferon (IFN)-alpha, because mRCC is largely resistant to chemotherapy [2].

One of the exciting developments in mRCC research has been a better understanding of the molecular pathogenesis of clear cell RCC, the most common histologic variant. It involves von Hippel-Lindau (VHL) tumor suppressor gene inactivation. Normally VHL encodes a protein that is a component of a ligase for hypoxia-inducible factor (HIF). Under normal oxygen tension, ligase action inactivates HIF. Under hypoxic conditions or with VHL inactivation, HIF upregulates the transcription of multiple hypoxia-inducible genes, including those encoding vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-alpha, and others that promote angiogenesis and cellular proliferation [3].

Both hereditary and sporadic mutations are associated with RCC development [4–5]. Four distinct types of hereditary RCC have been identified and linked to a genetic mutation: von Hippel-Lindau (VHL) syndrome, VHL tumor suppressor gene (chromosome 3p24-25); hereditary papillary renal carcinoma, c-MET proto-oncogene (chromosome 7q31-34); hereditary leiomyomatosis RCC, fumarate hydratase gene (chromosome 1q42.3-45); and Birt-Hogg-Dubé (BHD) syndrome, BHD tumor suppressor gene (chromosome 17p11.2). VHL gene mutations also occur in 70 % of sporadic clear cell RCC [4–5], and as clear cell RCC represents 80–85 % of all cases of RCC [6], VHL gene mutations are the most common genetic abnormality linked to RCC development.

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Authors and Affiliations

  1. Department of Medical Oncology, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif, France

    Bernard Escudier M.D. & Laurence Albiges M.D.

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  1. Bernard Escudier M.D.
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  2. Laurence Albiges M.D.
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Correspondence to Bernard Escudier M.D. .

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Editors and Affiliations

  1. Taussig Cancer Center, Cleveland Clinic, Pepper Pike, Ohio, USA

    Ronald M. Bukowski

  2. Division of Hematology Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Robert A. Figlin

  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Robert J. Motzer

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Escudier, B., Albiges, L. (2015). Anti-VEGF and VEGFR Monoclonal Antibodies in RCC. In: Bukowski, R., Figlin, R., Motzer, R. (eds) Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1622-1_11

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  • DOI: https://doi.org/10.1007/978-1-4939-1622-1_11

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