Resistance Mechanisms to Taxanes and PARP Inhibitors in Advanced Prostate Cancer

Curr Opin Endocr Metab Res. 2020 Feb:10:16-22. doi: 10.1016/j.coemr.2020.02.006. Epub 2020 Feb 19.

Abstract

The clinical landscape concerning advanced prostate cancer is rapidly changing and reaching beyond androgen deprivation therapy and androgen receptor targeted therapies. Taxane chemotherapy is a critical tool in the management of advanced prostate cancer. Additionally, novel drug classes such as PARP inhibitors are being investigated. Despite tremendous progress, resistance to therapy remains as a major impediment to further improvement. Resistance mechanisms appear diverse and are not fully known or understood. This review will highlight recent advances in research regarding mechanisms of resistance to both taxanes (such as increased drug efflux capacity) and PARP inhibitors (such as reversion mutations which restore DNA-repair proficiency). Understanding resistance to therapy promises to remove barriers blocking progress toward improved patient outcomes.

Keywords: Cabazitaxel; Docetaxel; Olaparib; PARP inhibitor; Resistance; Taxane.