Targeted therapies for prostate cancer

Abstract

The development of targeted therapies for prostate cancer has exploited various elements of prostate biology. The androgen-dependence of prostate cancer continues to be the focus for the development of new drugs and the analysis of details of the intermolecular interactions of the androgen receptor. Importantly, new applications of androgen ablation therapy have proven to have the greatest effect on cause-specific and overall survival during the last decade. Prostate epithelial cells express a number of tissue-specific proteins that have been the target either for antibody-directed therapies, in the case of prostate-specific membrane antigen, or target-activated therapies in the case of prostate-specific antigen, a serine protease. Prostate-specific proteins have also been targeted by the development of vaccines that have entered clinical trials. Humanized monoclonal antibodies and small molecules designed to inhibit oncogenic signalling pathways have been subjected to clinical trials in prostate cancer with limited success. The application of pathway inhibitors to prostate cancer therapy has been limited because no common dominant oncogenic mutation affecting signal kinase activation in prostate cancer has yet been identified. The interaction of signal kinase inhibitors with androgen ablation and with cytotoxic chemotherapy remains to be explored.

The Complex Role of AR Signaling After Cytotoxic Insult: Implications for Cell Cycle Based Chemotherapeutics

“…1). [10][11][12] Hormone therapy regimens designed to ablate AR activity are initially effective in almost all patients, and clinical response is most easily monitored by reduction in serum PSA (prostate specific antigen) levels. This observation is significant, as PSA is a direct AR target gene that is used clinically to monitor both disease development and progression.…”

Molecular Mechanism of Nkx3.1 Deregulation and Its Function in Murine Pten Prostate Cancer Model

“…These results suggest that concurrent PTEN and NKX3.1 down regulation act synergistically to promote prostate cancer initiation, but that the dosage of PTEN plays a critical role in this cooperative effect. (Asatiani and Gelmann, 2005) and histone modification (Plass, 2002), are all potential possibilities by which NKX3.1 is regulated by PTEN in our mouse model and merit further study.…”

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

“…This drug combines SERCA inhibitor thapsigargin and a target peptide called prostate-specific antigen (PSA). The toxicity of a smart bomb has been reported in PSA-positive PC cells [Asatiani and Gelmann, 2005]. The occurrence of splice variants characterizes many Ca 2+ channels and transporters found on the cell and ER membrane, and these variants may exhibit differential expression in normal and cancer cells [Leanza et al, 2016].…”