| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2005: ¥7,900,000 (Direct Cost: ¥7,900,000)
|
|---|
| Research Abstract |
Angiogenesis is an important therapeutic target in cancer and, to fully exploit its therapeutic potential, combinatorial chemotherapeutic/antiangiogenic regimens should be optimized and delivered earlier to more patients. Ideally, this could be done by a single potent, oral agent with established safety. Endostatin, an endogenous antiangiogenesis agent, inhibits tumor growth in several animal models without inducing resistance, and became the first to enter into human clinical trials. In human microvascular endothelium, we previously demonstrated that endostatin markedly down-regulates a variety of angiogenesis-related genes and up-regulates antiangiogenic genes, thereby inhibiting endothelial cell migration. Although tumor growth can be stunted by a variety of single angiogenesis inhibitors, combination antiangiogenesis protocols can be more effective than single agent therapies. Successful clinical application of angiogenesis inhibitors, irrespective of monotherapy or combination therapy, requires long-term administration, but most of them entering clinical trials are costly, large molecular weight proteins requiring parenteral administration. In the present study, we selected several ansamycin antibiotics as most promising cancer dormant therapeutic agents among many chemicals and peptides. They exert potent anti-angiogenesis effects, in addition to direct tumor-suppresive effects both in vitro and in vivo experimental systems. Clinical proof of concept study is now being planned using the most promising reagent.
|
