Acquired resistance to Docetaxel precedes fatality in hormone-refractory prostate cancer (HRPC).
However, strategies that target Docetaxel resistant cells remain elusive. Using in vitro and in vivo models, we identified a subpopulation of cells that survive Docetaxel exposure. This subpopulation lacks differentiation markers and HLA class I (HLAI) antigens, while overexpressing the Notch and Hedgehog signaling pathways. These cells were found in prostate cancer tissues and were related to tumor aggressiveness and poor patient prognosis. Notably, targeting Notch and Hedgehog signaling depleted this population through inhibition of the survival molecules AKT and Bcl-2, suggesting a therapeutic strategy for abrogating Docetaxel resistance in HRPC. Finally, these cells exhibited potent tumor-initiating capacity, establishing a link between chemotherapy resistance and tumor progression.
Written by:
Domingo-Domenech J, Vidal SJ, Rodriguez-Bravo V, Castillo-Martin M, Quinn SA, Rodriguez-Barrueco R, Bonal DM, Charytonowicz E, Gladoun N, de la Iglesia-Vicente J, Petrylak DP, Benson MC, Silva JM, Cordon-Cardo C. Are you the author?
Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Reference: Cancer Cell. 2012 Sep 11;22(3):373-88.
doi: 10.1016/j.ccr.2012.07.016
PubMed Abstract
PMID: 22975379
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