Abstract #5564: BNC105 is a tubulin targeting agent that is not susceptible to efflux by Pgp transporter expression, and yields additive therapeutic benefit when combined with other anti-cancer agents

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO BNC105 is a novel tubulin targeting agent that exhibits very high anti-tumor efficacy. BNC105 elicits a high rate of tumor regressions and tumor burden clearance in many human tumor xenograft models. We have previously shown that BNC105 exerts its anti-tumor activity through a dual mode of action. This agent selectively disrupts the vasculature in tumors, and additionally acts as a direct cytotoxic against cancer cells. In order to address the potential utility of BNC105 in cancer cells that develop resistance to chemotherapeutics through upregulation of efflux pumps, we investigated BNC105 activity in the presence of the efflux pump inhibitor, verapamil. Our data show that in a number of cell lines the efficacy of tubulin targeting agents commonly used in the clinic is reduced by the expression of efflux pumps. In contrast, BNC105 activity is not altered by efflux pumps suggesting that BNC105 is not susceptible to this drug resistance mechanism. Furthermore, we have investigated the capacity of BNC105 to be combined with other anti-cancer therapies. The potential for additive or synergistic effect between BNC105 and other agents was investigated using proliferation inhibition assays with a panel of human cancer cell lines. These assays suggest a strong synergistic effect of BNC105 with several anti-cancer agents including carboplatin, cisplatin, and 5-fluorouracil. The results of the subsequent investigation of these combinations in mouse xenograft assays concurred with our observations in cell lines. Furthermore, combination of BNC105 with radiotherapy treatment in a xenograft model of human head and neck cancer demonstrated a clear additive therapeutic benefit. BNC105 is currently under investigation in a phase I clinical trial. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5564.