Bfgf As A Therapeutic Target For Chemosensitization In Colorectal Cancer.

Proc Amer Assoc Cancer Res, Volume 47, 2006 5510 Our laboratory has shown that two fibroblast growth factors (aFGF and bFGF) expressed in solid tumors induce broad-spectrum resistance to anticancer drugs with diverse chemical structures and action mechanisms. We further showed that nontoxic doses of suramin, a nonspecific inhibitor of these growth factors, enhanced the anti-tumor activity of chemotherapeutic agents in breast, prostate, bladder and lung tumors. As advanced colorectal tumors express high levels of FGFs, the present study evaluated whether FGF antagonists enhance the activity of chemotherapy. The hypothesis was tested using the human HT-29 colon xenograft model and FGF antagonists (monoclonal antibodies to aFGF and bFGF, and nontoxic suramin). FGF antibodies were injected intratumorally, whereas CPT-11 and suramin were administered systemically. The results showed that the FGF antagonists, when administered alone, had no antitumor activity. However, when used in combination with CPT-11, anti-bFGF antibody or nontoxic suramin significantly enhanced the therapeutic efficacy (increased apoptotic index and median survival time, p<0.05). These benefits were attained without increasing the body weight loss. We further found that anti-bFGF antibody or suramin suppressed the expression of phosphorylated FGF receptors and survivin. These data support bFGF as a potential therapeutic target for chemosensitization in colon cancer. Supported in part by R01CA97067 and R01CA100922, NCI, DHHS.