Exploring a Novel Mechanism of Docetaxel Resistance in Prostate Cancer
Annual rept. 1 Mar 2012-28 Feb 2013
UNIVERSITY OF SOUTH ALABAMA MOBILE
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Docetaxel DTX, a semi-synthetic analog of paclitaxel, has emerged as the standard of care for chemotherapy of hormone-resistant prostate cancer. Docetaxel confers its anti-neoplastic activity by inhibiting microtubule depolymerization, which leads to G2M mitotic arrest and subsequent apoptosis 1. However, most patients treated with DTX ultimately develop resistance to the drug and succumb to the disease 2. Therefore, understanding the mechanisms underlying DTX resistance is a priority area in prostate cancer research. Previously, it was reported that CXCL12CXCR4 signaling play an important role in microtubule organization in immune cells 3 and its inhibition induced mitotic catastrophe G2M arrest in ovarian cancer cells 4. Based on these earlier observations, we hypothesized that CXCL12-CXCR4 signaling axis would promote docetaxel resistance by counteracting the microtubule stabilizing action of docetaxel.
- Anatomy and Physiology
- Medicine and Medical Research