David Mulholland

About David Mulholland

Evaluating the contribution of AR deficient stem/progenitor cells in Castrate Resistant Prostate Cancer

The use of anti-androgens is standard treatment for prostate cancer patients in the management of PSA recurrence and metastatic disease. However, all men with metastatic prostate cancer become castrate resistant (CRPC) during which time conventional androgen deprivation therapy is no longer effective. This indicates that cancerous cells may become less reliant upon androgen or androgen receptor (AR) mediated signaling and more dependent upon alternative survival pathways either as a consequence of treatment or during the natural disease evolution.

Recent studies on stem cells in in vitro experimental systems have shown that the deletion of important housekeeping genes can give rise to castration-resistant prostate cancerous tumors. In an extension to these observations, Dr. Mulholland proposes to study whether stem/progenitor cells with tumorigenic capabilities may acquire independence from the androgen/AR signaling axis and whether such cells are a potential source of the initiation of prostate cancer or the progression of aggressive metastatic prostate cancer. The short term goal of this proposal is to ascertain whether cancer initiating cells with impaired AR function can reconstitute disease progression in a manner that is entirely autonomous from AR function. The long term goal is the identification of alternative survival pathways, and therefore relevant targets, for cancers that are non-responsive to anti-androgen therapy.