Inhibition of Histone Deacetylases (HDACs) and mTOR Signaling: Novel Strategies Toward the Treatment of Prostate Cancer

Career Goals: With my background in tumor biology, cancer therapeutics, apoptosis, and translational research, the opportunity to develop this project in the Prostate Program at Roswell Park Cancer Institute offers me a great opportunity to positively impact my training and development as a postdoctoral fellow in the field of prostate cancer research. Furthermore, my work will provide opportunities for clinical application, and extend my knowledge of the involvement of epigenetics and the use of targeted therapies in prostate cancer. This training opportunity will facilitate my transition to an independent researcher in the field of prostate cancer research.

Objectives and Rationale: Current therapies for prostate cancer patients involve surgery, radiation, and hormone ablation. Unfortunately, these therapies provide promising short-term survival for patients, but often patients relapse with disease that is resistant to further treatment and is terminal for patients. Recent advances in the understanding of mechanisms that drive prostate cancer have identified particular proteins and pathways, in particular histone deacetylases (HDACs) and the mTOR pathway, respectively. HDACs regulate the expression of genes and proteins, and their deregulation in prostate cancer is still a mystery and needs to be better understood, while the mTOR pathway is involved in cell growth and proliferation and is often activated in prostate cancer. Excitingly, these identified proteins can be directly targeted by newly developed therapies. The research in this project will aim to increase our knowledge of HDAC and mTOR involvement in prostate cancer development and progression, and test the hypothesis that these novel targeted therapies in combination will offer new treatment options for patients who are resistant to current therapies available in the clinic.

Clinical Application: This research project aims to help patients at multiple stages of prostate cancer development. First, by stratifying the involvement of HDACs and mTOR, we may identify novel biomarkers or genetic signatures which allow detecting and treating primary prostate cancer at a much earlier stage than is currently available in the clinic. Second, by developing novel treatments, we can offer prostate cancer patients new therapy interventions which are relatively non-toxic and that can either be used in conjunction with current therapies or by themselves. Finally, this research will be conducted concurrent with Phase I clinical trials, thereby providing a perfect platform to translate data back and forth from bench to bedside and delineate where this therapy can be most effectively used, which can be of maximum benefit to prostate cancer patients.