Characterization of Epigenetic Regulatory Drivers of Prostate Cancer Metastasis

Objective and Rationale: The principal cause of cancer death in men is due to metastasis from prostate cancer. 'Metastasis' refers to a process by which the tumor, initially confined to the prostate, spreads to other organs such as bone, liver, or lung. Sadly, metastasis is not curable and most men succumb to the disease. Despite deep investigation directed to explore the origin of prostate cancer, less is known about the origin and progression of metastasis. There are many open questions on how the metastasis can originate from tumors and which mechanisms contribute to its formation. Therefore, an urgent issue is to investigate the mechanisms that promote the formation of metastasis. For example, changes in gene expression are known to be important to promote prostate cancer and the most important changes can be operated by factors that we call 'epigenetic drivers' -- we call them 'drivers' to distinguish them from passengers -- the drivers are the genes that are responsible to induce the metastatic process. However, little is known about the contribution of the epigenetic drivers to metastasis formation. So, in the proposed research plan it is our goal to identify these epigenetic 'drivers' in a way to improve the whole knowledge of metastasis, as well as the factors that influence its formation. Our study will characterize these epigenetic drivers with a promise to provide a rationale to design novel strategies directed at targeting those drivers for the management and prevention of metastasis.

Career Goals, Training Plan and Mentoring Plan: I am strongly motivated to pursue a career in prostate cancer research to improve my knowledge of this critical and often fatal disease. My principal goal is to investigate the molecular mechanisms underlying prostate cancer progression with the future promise of using this knowledge to develop novel approaches for prevention and management of metastatic prostate cancer. To meet this goal, for my postdoctoral training I have chosen the laboratory of Dr. Cory Abate-Shen, an excellent and committed prostate cancer researcher with significant experience in the generation of mouse models of prostate cancer. In the context of my proposed research, I will use mouse models of advanced stages of prostate cancer, which represent an excellent resource to explore the molecular aspects of the disease progression.

As my mentor and supporter, Dr. Cory Abate-Shen has a long history of successful training of post-doc fellows in the context of a stimulating research environment in the Columbia University Medical Center. Under her expertise and guidance, I will receive complete and effective training in all the responsibilities that are required to become an independent academic investigator, with the possibility to excel my expertise in the field of prostate cancer metastasis.

Ultimate Applicability of the Research: In my proposed project, I will use mouse models of prostate cancer to explore the 'epigenetic drivers' that could be relevant for the progression of the disease. We expect that our findings will identify the specific epigenetic drivers that can be targeted for the development of future drugs directed to inhibit metastatic growth. Furthermore, the results of our study could be helpful in the future for new therapies directed at patients with aggressive disease who are prone to develop metastases.

Contributions to Advancing the Field of Prostate Cancer Research: My entire study will impact the current knowledge of the most profound aspects of the disease, since I will dissect the concept that epigenetic drivers are responsible for the formation of metastasis. My study will unveil novel information that will help to distinguish tumors from metastases based on the action of epigenetic drivers. Their characterization will provide novel tools to combat metastasis both in terms of finding novel biomarkers for the early detection of metastasis and also targets to design therapeutic approaches for prostate cancer patients with advanced disease.