Abstract 681: PTX-008, a novel galectin-1 targeting agent, improves the effects of cytotoxic drugs in colon cancer cells

Abstract

Abstract Background: Addition of targeted therapies has been shown to potentiate the activity of cytotoxic drugs. Compounds with innovative mechanism of action such as PTX-008, a novel galectin-1 targeting agent, might represent an interesting candidate for cytotoxic-based combinations. We explored the effect of PTX-008 in combination with several drugs commonly used in cancer chemotherapy such as cisplatin, oxaliplatin, 5-FU, 5’-DFUR, taxotere and gemcitabine in colon cancer cell lines. Methods: Antiproliferative effects were evaluated in two human colon (Colo205 and HT29) cancer cell lines by MTT assay. Effects of different schedules of exposure of PTX-008-based combinations were determined by median effect plot analysis (Chou & Talalay). Results: PTX-008 induced significant growth inhibition at concentrations below 10 µM in HT29 and Colo205 cancer cell lines. Combination of PTX-008 with cisplatin and oxaliplatin was additive or synergistic in both Colo205 and HT29 cells for all administration schedules. Combination of PTX-008 with antimetabolites 5-FU and 5’-DFUR was synergistic for sequential administration schedule, especially when PTX-008 was given prior to 5-FU and 5’-DFUR in colon cancer cells. Simultaneous exposure to these drugs induced additive effects. Combination with taxotere was at least additive using all schedules of administration. PTX-008/gemcitabine combination were highly synergistic in Colo205 and HT29 cells for sequential schedules and additive/synergistic for simultaneous administration. Conclusions: Combination studies showed that PTX-008 displays at least additive, often synergistic effects with a wide range of cytotoxic drugs (including cisplatin, oxaliplatin, 5-FU, gemcitabine and taxotere). Those data provide preliminary evidences that inhibition of galectin-1 using PTX-008 may be an attractive approach for combinations with anticancer drugs in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 681. doi:10.1158/1538-7445.AM2011-681