Integrated Therapeutic Targeting of the Prostate Tumor Microenvironment

Prostate cancer is a common and deadly cancer among men. The heterogeneity that characterizes prostate tumors contributes to clinical challenges in the diagnosis, prognosis, and treatment of this malignancy. While localized prostate cancer can be treated with surgery or radiotherapy, metastatic disease to the lymph nodes and the bone requires aggressive treatment with androgen deprivation treatment (ADT). Unfortunately, this often eventually progresses to metastatic castration-resistant prostate cancer (mCRPC). Advanced prostate cancer treatment today involves 1st- and 2nd-line taxane chemotherapy and 2nd-generation antiandrogens. The process of epithelial mesenchymal transition (EMT), during which epithelial cells lose their adhesions and their polarity, is a critical contributor to prostate cancer metastasis. In this article, we aim to integrate the current understanding of mechanisms dictating the dynamics of phenotypic EMT, with apoptosis outcomes in prostate tumors in response to antiandrogen and taxane chemotherapy for the treatment of advanced disease. Novel insights into the signaling mechanisms that target the functional interface between apoptosis and EMT will be considered in the context of potential clinical markers of tumor prognosis, as well as for effective therapeutic targeting of α- and β- adrenergic signaling (by novel and existing chemotherapeutic agents and antiandrogens). Interfering with EMT and apoptosis simultaneously toward eradicating the tumor mass is of major significance in combating the lethal disease and increasing patient survival.