Enhancing Chemotherapy Efficacy in Pten -Deficient Prostate Tumors by Activating the Senescence-Associated Antitumor Immunity

• DOI: 10.1016/j.celrep.2014.08.044
• Publication Date: 2014-09-25T15:51:34Z
• Authors: Alberto Toso; Ajinkya Revandkar; Diletta Di Mitri; Ilaria Guccini; Michele Proietti; Manuela Sarti; Sandra Pinton; Jiangwen Zhang; Madhuri Kalathur; Gianluca Civenni; David Jarrossay; Erica Montani; Camilla Marini; Ramon Garcia-Escu...; Eugenio Scanziani; Fabio Grassi; Pier Paolo Pandolfi; Carlo V. Catapano; Andrea Alimonti
• Keywords: Senescence

Prosenescence therapy has recently emerged as a novel therapeutic approach for treating cancer. However, this concept is challenged by conflicting evidence showing that the senescence-associated secretory phenotype (SASP) of senescent tumor cells can have pro- well antitumorigenic effects. Herein, we report that, in Pten-null tumors, activation Jak2/Stat3 pathway establishes an immunosuppressive microenvironment contributes to growth and chemoresistance. Activation tumors sustained downregulation protein tyrosine phosphatase PTPN11/SHP2, providing existence PTEN/SHP2 axis. Importantly, treatment with docetaxel combination JAK2 inhibitor reprograms SASP improves efficacy docetaxel-induced senescence triggering strong antitumor immune response tumors. Altogether, these data demonstrate surveillance be suppressed specific genetic backgrounds but also evoked pharmacological treatments.