Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors
Alessandro Alaimo, Marco Lorenzoni, Paolo Ambrosino, Arianna Bertossi, Alessandra Bisio, Alice Macchia, Eugenio Zoni, Sacha Genovesi, Francesco Cambuli, Veronica Foletto, Dario De Felice, Maria Virginia Soldovieri, Ilaria Mosca, Francesco Gandolfi, Matteo Brunelli, Gianluca Petris, Anna Cereseto, Álvaro Villarroel, George N. Thalmann, Francesco Giuseppe Carbone, Marianna Kruithof‐de Julio, Mattia Barbareschi, Alessandro Romanel, Maurizio Taglialatela, Andrea Lunardi
Abstract
Abstract Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca 2+ cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.