Abstract
<div>Abstract<p>To examine the potential of combining Bcl-2 family inhibitors with chemotherapy in ovarian cancer, we evaluated a panel of 27 ovarian cancer cell lines for response to the combination of navitoclax (formerly ABT-263) and paclitaxel or gemcitabine. The majority of cell lines exhibited a greater than additive response to either combination, as determined by the Bliss independence model, and more than 50% of the ovarian cell lines exhibited strong synergy for the navitoclax/paclitaxel combination. To identify biomarkers for tumors likely to respond to this combination, we evaluated the protein levels of intrinsic apoptosis pathway components. Bcl-x<sub>L</sub> seems necessary, but not sufficient, for navitoclax/paclitaxel synergy <i>in vitro</i>, suggesting that exclusion of patients whose tumors have low or undetectable Bcl-x<sub>L</sub> would enrich for patients responsive to the combination. We evaluated Bcl-x<sub>L</sub> levels in ovarian cancer tumor tissue from 40 patients (20 taxane responsive and 20 with poor response to taxane) and found that patients with high Bcl-x<sub>L</sub> were less sensitive to taxane treatment (10 of 12) Bcl-x<sub>L</sub> positive patients, <i>P</i> = 0.014). These data support the use of navitoclax in combination with taxane-based therapy in ovarian cancer patients with high levels of Bcl-x<sub>L</sub>. <i>Mol Cancer Ther; 11(4); 1026–35. ©2012 AACR</i>.</p></div>
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call