Antiangiogenic (metronomic) chemotherapy for brain tumors: current and future perspectives.
Significant advances in the diagnosis and treatment of brain tumors have been made through better imaging, surgical techniques and advances in radiation therapy. However, the cure rate for most adult and pediatric brain tumor patients has not mirrored this success. Angiogenesis, the development of neovascularization, provides the required nutrients and oxygen to an expanding tumor and is controlled by a complex balance of proangiogenic cytokines and antiangiogenic factors. A series of new inhibitors of angiogenesis are now in clinical trials. Most of these rely on inhibiting tumor cell-mediated cytokines or blocking the activation of their cognate receptors. Cytotoxic chemotherapy, by contrast, targets dividing cells but can be modulated to attack dividing endothelial cells. This review will focus on the use of low-dose antiangiogenic (also called metronomic) chemotherapy to inhibit endothelial cell function and resultant neovascularization in the treatment of adult and pediatric brain tumors. By examining the biology and preclinical findings that led to the development of antiangiogenic/metronomic chemotherapy, clinical studies have been undertaken that support the role of this approach in the clinic, and have led to the introduction of a number of markers being used to better predict active combinations and appropriate patient populations.
Samuel
David P
DP
Harvard Medical School, Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute and Children's Hospital of Boston, Boston, MA 02115, USA.
Wen
Patrick Y
PY
Kieran
Mark W
MW
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000639:trends; D004334:Drug Administration Schedule; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents