The emerging quest for the optimal angiostatic combination therapy.
Angiostatic therapies are now routinely embedded in the daily clinical management of cancer. Although these agents clearly benefit patient survival rates, the effect is only moderate with sometimes considerable side effects. A major cause of failure in this respect is the induction of resistance and tolerability against these drugs. Most angiostatic drugs are tyrosine kinase inhibitors that aim to inhibit or neutralize the activity of tumour-produced growth factors. Frustrating the tumour cells in this way results in genetic adaptations in the cells, turning them into mutants that are dependent on other growth mechanisms. It may therefore be necessary to shift to another class of drugs that directly target the tumour vasculature. It is evident that improvement of future angiogenesis inhibitors can only arise from two efforts. First, through the identification of better targets, preferably specifically expressed in the tumour vasculature. Secondly, through the development of combination therapies. The present review highlights the current efforts and challenges in trying to develop effective angiostatic combination therapies.
*Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
Arjan W
AW
Griffioen
Andrea
A
Weiss
Robert H
RH
Berndsen
*Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
U Kulsoom
UK
Abdul
*Angiogenesis Laboratory, Department of Medical Oncology, VU Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
Marije T
MT
te Winkel
Patrycja
P
Nowak-Sliwinska
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010778:Photochemotherapy
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents