Antiangiogenic cancer therapies get their act together: current developments and future prospects of growth factor- and growth factor receptor-targeted approaches.
Targeting the vascular endothelial growth factor (VEGF) in combination with standard chemotherapy has recently proved successful in the treatment of different types of advanced cancer. The achievements of combinatorial anti-VEGF monoclonal antibody bevacizumab (BEV) renewed the confidence in targeted antiangiogenic approaches to constitute a complementary therapeutic modality in addition to surgery, radiotherapy and chemotherapy. While several second-generation multitargeted tyrosine kinase inhibitors show promise in defined tumor entities, these novel antiangiogenic compounds have yet to meet or exceed the efficacy of combinatorial BEV therapy in ongoing clinical trials. Current developments of targeted antiangiogenic agents include their use in the adjuvant setting and the combination of different antiangiogenesis inhibitors to take a more comprehensive approach in blocking tumor angiogenesis. The identification of surrogate markers that can monitor the activity and efficacy of antiangiogenic drugs in patients belongs to the most critical challenges to exploit the full potential of antiangiogenic therapies. The opportunities and obstacles in further development of growth factor- and growth factor receptor-targeted antiangiogenic approaches for advanced cancer, including malignant melanoma, will be discussed herein with particular reference to selected ongoing clinical trials.
Department of Dermatology, Dermato-Oncology Unit, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. gille@em.uni-frankfurt.de
Jens
J
Gille
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003131:Combined Modality Therapy; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D004815:Epidermal Growth Factor; D020794:Receptor Protein-Tyrosine Kinases