Metastatic castration-resistant prostate cancer-emerging trends in therapy

Abstract

An increasing understanding of the cellular processes involved in growth, metastasis and development of resistance enable the development of new treatment strategies for advanced prostate cancer. Using selected examples, the aim of this report is to present current developments to the reader and to give an outlook on possible upcoming changes in the treatment of advanced prostate cancer. Narrative report based on expert consensus, supported by aliterature search in PubMed (MEDLINE) and the abstract databases of the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO). Examples were selected to illustrate current developments without claiming completeness. The androgen receptor (AR) signal transduction pathway remains afocus of scientific interest. Androgen synthesis inhibitors and AR degraders are promising new approaches to overcome resistance mediated by AR mutations or splice variants. Inhibition of key switch sites of alternative signaling pathways such as AKT or CDK4/6 provide additional treatment options, including combinational strategies through atight linkage with the AR signaling pathway. Abetter understanding of tumor microenvironment and immune response is required for novel immunotherapeutic strategies using bispecific T‑cell engagers (BiTEs) and chimeric antigen receptor (CAR) Tcells. New treatment strategies give hope that we will be able to intervene even more effectively in the course of disease of advanced prostate cancer in the future. However, amajor challenge, especially for the implementation of targeted treatment approaches, is likely to be the heterogeneity of tumor progression not only inter- but also intrapersonally.