Identification of novel therapeutic targets to selectively eliminate senescent cells in prostate cancer.

Despite recent progresses, prostate cancer (PC) is still the second most diagnosed cancer and the sixth leading cause of cancer death among men worldwide. Commonly used anticancer treatments to eradicate PC are based on chemotherapy and radiotherapy, with or without a castration-based strategy in which androgen deprivation is achieved by pharmacological or surgical castration. Efficacy of all these types of therapies also rely on their abilities to induces “premature” senescence, a cellular state characterized by the irreversible arrest of cell growth that affects both normal and cancer proliferating cells. However, despite the proliferation block, senescent cells remain metabolically and synthetically active: indeed, they release many cytokines and chemokines known as senescence-associated secretory phenotype (SASP) able to affect nearby cells. In particular conditions, SASP may promote cellular proliferation and angiogenesis thus inducing tumour progression and invasiveness. For this reason, elimination of senescent cells from tumours can avoid cancer metastasis and relapse. In our study, starting from a proteomic and bioinformatic analysis of FDG-based FACS-sorted PTEN null murine prostate tumour cells, we identify membrane proteins upregulated on senescent population that can be exploited as potential targets for the development of new therapeutic strategy for senescent cells clearance.