Approximately a quarter of aggressive prostate cancers progress to a lethal disease due to the emergence of resistance to androgen deprivation therapy. The cancer stem cell hypothesis proposes that a rare subpopulation of cells within a tumor possesses the key features of stem cells, namely self-renewal and multi-potency, and that these stem-like cancer cells arise from oncogenic transformation of normal stem cells or closely related multi-potent progenitors.
The aim of the project is to identify the pre-existing stem/progenitor-like PCa cells based on differential resistance to castration for survival and/or growth and specific stem cell markers. To this purpose, we are using an androgen-dependent (BM18) and an androgen-independent (LAPC9) PDX models to isolate cancer stem cells. Our goal is to expand our understanding of the molecular mechanisms controlling intrinsic resistance to androgen deprivation therapy, by characterizing these subpopulations of cancer stem-like cells from a genomic and transcriptomic point of view. Such information will be important for understanding why prostate cancer relapse as castration resistant prostate cancer and for developing better treatments for castration resistant prostate cancer. Additionally, these studies could lead to the identification of novel mechanisms of castration resistance that could be translated into biomarkers able to distinguish indolent from aggressive prostate cancer and provide surrogate end-point markers for monitoring prostate cancer treatments.