Author/Authors :
Eva Domingo-Domènech، نويسنده , , Josep and Vidal، نويسنده , , Samuel J. and Rodriguez-Bravo، نويسنده , , Veronica and Castillo-Martin، نويسنده , , Mireia and Quinn، نويسنده , , S. Aidan and Rodriguez-Barrueco، نويسنده , , Ruth and Bonal، نويسنده , , Dennis M. and Charytonowicz، نويسنده , , Elizabeth and Gladoun، نويسنده , , Nataliya and de la Iglesia-Vicente، نويسنده , , Janis and Petrylak، نويسنده , , Daniel P. and Benson، نويسنده , , Mitchell C. and Silva، نويسنده , , Jose M. and Cordon-Cardo، نويسنده , , Carlos، نويسنده ,
Abstract :
Summary
ed 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.
