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Activity of the multikinase inhibitor dasatinib against ovarian cancer cells
British Journal of Cancer, 11/02/09

Konecny GE et al. – These data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer.

Methods

Examined effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using panel of 34 established human ovarian cancer cell lines
Molecular markers for response prediction studied using gene expression profiling
Multiple drug effect/combination index (CI) isobologram analysis was used to study interactions with chemotherapeutic drugs

Results

Concentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to 3 log-fold difference in IC50 values
Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest
At wide range of clinically achievable drug concentrations, additive and synergistic interactions observed for dasatinib plus carboplatin or paclitaxel
24 out of 34 (71%) representative ovarian cancer cell lines highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported
Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA particularly sensitive to dasatinib

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