Studying the Cell Cycle's Role in the Transdifferentiation of Prostate Cancer

Prostate cancer (PC) is the second most common cancer in men worldwide, affecting 58 men daily in Canada. As treatment options continue to evolve, disease management and overall patient outcomes have improved. While effective, these treatments can sometimes pressure PC cells to transdifferentiate into a more aggressive, treatment resistant type of PC, known as neuroendocrine prostate cancer (NEPC). Treatment options for NEPC are very limited as it is resistant to all current therapies, leading overall prognosis to remain very poor with an estimated survival of less than one year. Further, the mechanism behind the progression of disease to NEPC remains limited, with few markers being used to study progression. Our lab has identified a class of cell cycle regulatory proteins elevated in NEPC, with evidence supporting that these proteins have the potential to drive progression to this drug-resistant form of disease. This project aims to establish a PC to NEPC platform of disease progression to study the specific role of these regulatory proteins during PC transdifferentiation. Further, we will utilize drugs that can block these proteins and test whether these drugs can treat and/or prevent the progression of disease to NEPC. This work will be completed using in vitro and in vivo models, including cells, animal, and human samples. Preventing the progression of disease to NEPC and identifying markers of NEPC remains one of the greatest challenges in this field, and we have strong rationale and data to support this being a promising direction that could make a meaningful impact.