E14605 Background: Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone, and are HER-2 normal. TNBC cell lines have displayed greater sensitivity to growth inhibition by the multi-target kinase inhibitor, dasatinib, than luminal or HER- 2 positive breast cancer cell lines. The aim of this study was to assess the direct anti-tumor effects of dasatinib in combination with chemotherapy in TNBC. Methods: Four TNBC cell lines (MDA-MB-231, HCC-1143, HCC-1937, MDA-MB-468) were treated with dasatinib in combination with docetaxel, cisplatin or 5'-5' DFUR. IC50 values were calculated for each drug alone by determining response in a 5-day proliferation (acid phosphatase) assay. Combination index (CI) values were determined, using CalcuSyn, to assess the interaction between drugs. Results: Three of the cell lines (MDA-MB-231, HCC- 1143, HCC-1937) were sensitive to dasatinib (IC50 < 1 μM) whereas MDA-MB-468 was resistant (IC50 > 1 μM) (Table). In MDA-MB-231 and HCC-1143 cells, combined treatment with dasatinib and 5'-5'-DFUR displayed synergy (CI<1.0), whereas the combination was additive in HCC-1937 cells (CI=0.98). Combined treatment with dasatinib and cisplatin was synergistic in the three dasatinib sensitive cell lines (CI<1.0). Dasatinib in combination with docetaxel displayed moderate synergy in MDA-MB-231 and HCC-1937 cells (CI1.0). Conclusions: Our findings show that the combination of dasatinib with either 5'-5'-DFUR or cisplatin is synergistic in TNBC cell lines, and suggest that combinations of dasatinib with chemotherapy may improve response in triple negative breast cancer patients. [Table: see text] No significant financial relationships to disclose.