Targeting FOXM1 in Enzalutamide-Resistant Castration-Resistant Prostate Cancer

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths among males in Western countries. One in seven men will be diagnosed with prostate cancer in North America, and it has been estimated that globally 300,000 men die from it every year. Many patients will undergo therapies targeting androgens, which promote tumor growth. Inevitably, however, these patients develop lethal castration-resistant prostate cancer (CRPC), a disease that is especially drug-resistant. The emergence of CRPC is poorly understood. Recently, there have been a number of treatment breakthroughs that have resulted in decreased suffering and prolonged survival for men with CRPC. These advances include novel androgen receptor inhibitors such as Enzalutamide. Unfortunately, prostate cancer can rapidly become resistant to these new therapies, resulting in significant pain and suffering. In our laboratory, we study the responses of CRPC tumor cells to novel anti-prostate cancer therapies in an attempt to understand why they become drug-resistant and to identify molecular changes in the cells that may be targeted to improve CRPC treatments. We have developed unique ways to model drug-resistant CRPC using human prostate cancer cells. Growing these cells in mice treated with androgen suppressing therapy makes them drug-resistant, which we know occurs in CRPC patients. In this study, a novel, recently discovered mechanism that makes CRPC resistant to current therapies will be explored and targeted. This will hopefully improve survival of prostate cancer patients in the future.

I have a great passion for cancer research and a strong background in studying molecular mechanisms and identification of novel treatment options for prostate cancer. My goal is to become an independent principal investigator exploring the mechanisms and targeting prostate cancer especially in its treatment-resistant stage. During my PhD in Finland, I identified novel compounds for prostate cancer treatment and here at Vancouver Prostate Centre, my mentor Dr. Zoubeidi's unique Enzalutamide-resistant cell line and mouse models excited me as a smooth way to develop my career, explore the mechanisms of treatment resistance, as well as expand my horizons of clinical research. I hope I eventually will bring these novel discoveries from bench to bedside for prostate cancer treatment. My training plan will support my professional development by giving me opportunity to develop my skills in preclinical validation methods, mentor graduate and undergraduate students in our laboratory, attend important courses, and obtain skills that are essential when I will start my own research group after my postdoctoral period. My project will study the molecular mechanisms and target the key pathways in prostate cancer cells that have become resistant to current therapies. I will focus on compounds that are already in use and thus rapidly transferrable for prostate cancer patient treatment. In these preclinical validations, I hope I can confirm the reduction of prostate cancer cell growth and then bring these agents for prostate cancer patients currently lacking treatment options due to resistance.