Abstract:
Prostate cancer represents a leading cause of death in the male population. Nowadays the androgen deprivation therapy (ADT) represents the standard care for most prostate cancer patients, but after a median duration of response of 12–24 months under continuous ADT, most prostate tumors progress to castration-resistance prostate cancer (CRPC), a critical clinical condition with poor perspectives and no optional treatment. It is known that cancer growth and proliferation rely on intracellular iron availability. Iron has both beneficial and deleterious effects on tumor cells: although it is essential for cancer cell growth and proliferation,various studies have confirmed the pivotal role of ferroptosis, an iron-dependent form of cell death, in killing cancer cells and suppressing tumor growth.
In this research proposal, representing the continuation of an ongoing FUV fellowship, two opposite anticancer approaches will be explored: the first one using iron chelators to deplete cancer cells of iron, and the second, a more recent strategy, exploiting an iron overload treatment to facilitate the production of cytotoxic reactive oxygen species (ROS) within tumor leading to cell death (ferroptosis).
The availability of an integrated “prostate cancer platform” represented by the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) model and tumor cell line derived from this mouse model (TRAMP-C2), as well as of human androgen-dependent (LNCaP) and androgen-independent (DU145) prostate cancer cells, provide the opportunity to better characterize in vitro and in vivo the link between iron and prostate cancer. Moreover, combination therapy experiments will be carried out with TRAMP mice treated with Enzalutamide (MDV3100), a potent second generation androgen receptor antagonist approved for the treatment of CRPC, to understand how iron deprivation/overload may improve the efficacy of chemotherapeutic drugs or overcome the drug resistance onset.
Durata del progetto:
12 mesi
Responsabile scientifico: Dott.ssa Federica Maccarinelli
federica.maccarinelli@unibs.it
Dipartimento di Medicina Molecolare e Traslazionale