Early Detection of Castration-Resistant Prostate Cancer by Assessing Interactions between Circulating Tumor Cells and Accompanying Immune Cells

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. In majority of "castration sensitive" patients proliferation of cancer cells depends on supply of androgen and can be attenuated by the androgen deprivation therapy (ADT). Unfortunately, many patients develop "castration resistance" (CR), when the tumor growth and metastatic spread continue despite ADT. For effective second-line therapy that saves lives and improves life quality the resistance needs to be detected early. Circulating tumor cells (CTCs) that can be isolated from the standard blood sample are considered "seeds of metastasis". We postulate that mechanical and immunochemical profiling of CTCs and accompanying immune cells provide clues about CTCs aggressiveness and the risk of CR. Our specific aims call for determining the role of (1) epithelial-mesenchy transition (EMT) and (2) interactions with circulating macrophages in survival-promoting mechanical fitness of CTCs. Combing the cell culture studies with profiling of CTCs will lead to (3) construction of predictive model for early CR detection. In the third reporting period we completed a majority of tasks in accordance with the statement of work. The exception is patients' accrual, slowed down by the pandemic. The project now enters NCE phase to finish the collection and analysis of patents' samples. The outcomes for now include a paper published in Cancer research.