Anti-VEGF and VEGFR Monoclonal Antibodies in RCC View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2015

AUTHORS

Bernard Escudier , Laurence Albiges

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. More... »

PAGES

237-252

Book

TITLE

Renal Cell Carcinoma

ISBN

978-1-4939-1621-4
978-1-4939-1622-1

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-1-4939-1622-1_11

DOI

http://dx.doi.org/10.1007/978-1-4939-1622-1_11

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016961295


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