Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration-Resistant Prostate Cancer
Annual rept. 30 Sep 2013 29 Sep 2014
CALIFORNIA UNIV LOS ANGELES
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The purpose of this project is to evaluate the role of a rare subset of progenitor-like luminal cancer cells that may have special properties enabling them to resist standard therapies and mediate tumor recurrence. Our most significant accomplishment to date is identifying activated inflammatory signaling in these luminal progenitor cells. Blockade of this pathway depletes growth and survival of luminal progenitor cells by reducing expression of a number of important proliferative and anti-apoptotic factors including BCL2 and eIF4E. Over-expression of eIF4E, previously found to regulate luminal progenitor-like prostate cancer cells, can partially compensate for inhibition of NFkB signaling, suggesting that eIF4E and NFkB are both regulators of this rare cell population and may act as part of the same signaling pathway. Further understanding of these progenitor cells, the pathways they use to control their growth and survival, and the markers they uniquely express will allow us to identify and target these cells in order to predict, prevent or treat advanced castration-resistant prostate cancer.
- Medicine and Medical Research