Targeting angiogenesis in hepatocellular carcinoma: focus on VEGF and bevacizumab.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and one of the few malignancies with an increasing incidence in the USA. While the relationship between HCC and its inciting risk factors (e.g., hepatitis B, hepatitis C and alcohol liver disease) is well defined, driving genetic alterations are still yet to be identified. Clinically, HCC tends to be hypervascular and, for that reason, transarterial chemoembolization has proven to be effective in managing many patients with localized disease. More recently, angiogenesis has been targeted effectively with pharmacologic strategies, including monoclonal antibodies against VEGF and the VEGF receptor, as well as small-molecule kinase inhibitors of the VEGF receptor. Targeting angiogenesis with these approaches has been validated in several different solid tumors since the initial approval of bevacizumab for advanced colon cancer in 2004. In HCC, only sorafenib has been shown to extend survival in patients with advanced HCC and has opened the door for other anti-angiogenic strategies. Here, we will review the data supporting the targeting of the VEGF axis in HCC and the preclinical and early clinical development of bevacizumab.
Finn
Richard S
RS
Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 11-934 Factor building, Los Angeles, CA 90095, USA. rfinn@mednet.ucla.edu
Zhu
Andrew X
AX
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D000069287:Capecitabine; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000188:drug therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003603:Cytotoxins / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011687:Purines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003603:Cytotoxins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D011687:Purines; D011799:Quinazolines; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; C489254:AEE 788; D005472:Fluorouracil; D000093542:Gemcitabine