Angiogenesis inhibitors under study for the treatment of lung cancer.
Several classes of agents now exist that target the different steps involved in angiogenesis. These include drugs inhibiting matrix breakdown, the matrix metalloproteinase inhibitors (MMPIs), such as marimastat, prinomastat, BMS275291, BAY12-9566, and neovastat. Trials of this class of agents have all been negative to date. Drugs that block endothelial cell signaling via vascular endothelial growth factor (VEGF) and its receptor (VEGFR) including rhuMAb VEGF, SU5416, SU6668, ZD6474, CP-547,632 and ZD4190 are all in earlier stages of clinical trial. Drugs that are similar to endogenous inhibitors of angiogenesis including interferons have also been evaluated without success. Endostatin has been shown to have an acceptable toxicity profile, but clinical evidence of activity has not yet been demonstrated. There has also been renewed interest in thalidomide. Drugs such as squalamine, celecoxib, ZD6126, TNP-470 and those targeting the integrins are also being evaluated in lung cancer. Despite early enthusiasm for many of these agents, Phase III trials have not yet demonstrated significant increases in overall survival and toxicity remains an issue. It is hoped that as our understanding of the complex process of angiogenesis increases, so will our ability to design more effective targeted therapies.
Shepherd
Frances A
FA
Division of Hematology Oncology, Department of Medicine, University Health Network, Princess Margaret Hospital Division, University of Toronto, 610 University Avenue, Suite 5-104, Ont., M5G 2M9, Toronto, Canada. frances.shepherd@uhn.on.ca
Sridhar
Srikala S
SS
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005109:Extracellular Matrix; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors