Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Abstract

Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries. Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years. The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling. Although a partly remediation is accomplished at the beginning of treatment, some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching, from E-cadherin to Ncadherin, which is the hallmark of epithelial-mesenchymal transition. Diverse direct and indirect mechanisms are involved in this switching and consequently, the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells. Since E-cadherin represses invasive and migrative behaviors of the tumor cells, the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation. In this study, we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-β pathway.

Identification of cell differentiation trajectory-related gene signature to reveal the prognostic significance and immune landscape in prostate cancer based on multiomics analysis

“…The well-being of men is facing an escalating threat due to prostate cancer [ 40 , 41 ]. Following radical prostatectomy or chemoradiotherapy, a substantial proportion of patients—ranging from 27% to 53%—have been documented to experience BCR [ 5 ].…”

Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches

“…RNA expression of SPDEF, ERG, and Prostate Cancer Antigen 3 (PCA3) detected in urine samples outperformed mainstream markers in the prediction of PCa with high sensitivity and specificity to PCa [37]. The RNA levels of these same genes (SPDEF, ERG, and PCA3) when isolated from urine-derived exosomes can be used to predict the probability of a high-grade PCa without the necessity of a digital rectal exam (DRE) [36,[38][39][40][41]. The evaluation of these markers allied with the standard clinical criteria analysis increased by 30% the detection of high-grade PCa, thus improving patient stratification and medical practitioners' decision making [42].…”

Current status and progress of the development of prostate cancer vaccines

“…Androgen deprivation therapy (ADT) can induce T cells to activate prostate antigen and temporarily reduce the tolerance of T cells. A synergistic relationship between ADT and immunotherapy has been proposed 51 . So far FDA has authorized the use of ipilimumab monoclonal antibody as cancer immunotherapy.…”