Novel sensitizing agents: potential contribution of COX-2 inhibitor for endocrine therapy of breast cancer.

Enhancement of the therapeutic effect of conventional drugs is currently an active treatment strategy for breast cancer, as shown in the clinical application of trastuzumab with chemotherapeutic agents, which prolonged survival even for metastatic disease. Cyclo-oxygenase 2(COX-2)inhibitors, which are chemoprevention agents for familial polyposis coli, are now contributing to this strategy in combination with chemotherapeutic and endocrine drugs. As an endocrine application, overexpression of COX-2 contributes to increased expression of aromatase in the breast tumor. In addition, it is also known to promote rich micro-vessels within the tumor through up-regulation of prostaglandin E2(PGE2), which can induce vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in cancer cells, and can directly modulate endothelial cell proliferation. Since both rich vasculature and accelerated estrogen synthesis are thought to contribute to unfavorable conditions for the response to endocrine therapy, inhibiting COX-2 with COX-2 inhibitors is a promising strategy to potentiate endocrine therapy.