Targeting angiogenesis for the treatment of sarcoma.
OBJECTIVE
More therapeutic options are needed for bone and soft tissue sarcomas, especially for patients with metastatic disease. Recent randomized clinical trials conducted in colon, breast and lung cancer have shown the anti-vascular endothelial growth factor agent, bevacizumab, alone or in combination with chemotherapy, improves response and survival. Preclinical studies have demonstrated the anti-tumor effects of varied anti-angiogenic agents in sarcoma cell lines and tumor models.


RESULTS
Preclinical studies in sarcomas have evaluated the role of targeted agents including platelet-derived growth factor, matrix metalloproteinases, urokinase receptor and varied small-molecule tyrosine kinase inhibitors. Novel angiogenesis inhibitors are being studied in the treatment of sarcoma, including monoclonal antibodies against vascular endothelial growth factor, cis- and trans-retinoic acids, thalidomide, and tyrosine kinase inhibitors. Phase I, II and III clinical trials continue to evaluate these agents alone, in combinations together and combined with standard chemotherapy. We review herein the preclinical rationale and clinical trial results of anti-angiogenesis therapy in the treatment of soft tissue and bone sarcoma.


CONCLUSIONS
Preclinical mechanistic study and clinical trials are continuing in order to evaluate the therapeutic role and ultimately validate the efficacy of the varied anti-angiogenesis agents in soft tissue and bone sarcoma.
Balasubramanian
Lakshmi
L
Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA.
Evens
Andrew M
AM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002986:Clinical Trials as Topic; D006801:Humans; D009389:Neovascularization, Pathologic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012509:Sarcoma / Q000188:drug therapy*; D012514:Sarcoma, Kaposi / Q000378:metabolism; D013792:Thalidomide / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases