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Grants

Development of YB-1 as a therapeutic target in advanced prostate cancer

YB-1 is a major driver of prostate cancer progression and mediates castrate- and chemoresistance and as such is a promising therapeutic target in advanced prostate cancer.

This research project is founded on two transcriptome wide microarray studies that have identified YB-1 downstream targets on the transcriptional and post-transcriptional level in LNCaP prostate cancer cells. Combining these two datasets and cross-referencing them to prostate cancer transcriptional responses to androgens, anti-androgens and various treatments within the team’s large data repository, this research aims to establish a comprehensive picture of the cellular processes that YB-1 is controlling with a focus on pathways mediating castrate- and chemoresistance.

The research team has found that YB-1 controls a large subset of androgen responsive genes and could as such play a major role in the reactivation of androgen signalling during progression to castrate resistance. This research will determine the molecular mechanisms by which YB-1 regulates these targets, and study the biological processes that are co-regulated by YB-1 and androgens. Further investigation will be undertaken to determine how YB-1 contributes to the activation of castrate resistant tumour growth by affecting key players of proliferation and cell cycle control.

The research will also explore whether targeting YB-1 can enhance sensitivity of prostate cancer cells towards chemotherapeutic drugs, identify the key mediator molecules and the mechanism of their regulation by YB-1. These findings will open new avenues for combinatorial therapy of androgen targeted or chemotherapeutic agents with development of an innovative YB-1 targeted therapy for the treatment of advanced prostate cancer.

Investigators

Colleen Nelson APCRC-Q, IHBI, QUT, TRI

Associate Investigators

Melanie Lehman APCRC-Q, IHBI, QUT, TRI
Anja Rockstroh APCRC-Q, IHBI, QUT, TRI

Duration

2015 - 2016

Funding