Taxanes - docetaxel and cabazitaxel - are the most active chemotherapy drugs currently used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, despite a good initial response and survival benefit, nearly all patients eventually develop resistance, which is an important barrier to long-term survival. Resistance to taxanes is also associated with cross-resistance to androgen receptor signaling inhibitors (ARSIs). Unfortunately, other than platinum-based treatments, which have demonstrated some benefit in a subset of patients with Aggressive Variant Prostate Cancer (AVPC), few therapeutic options are available to patients progressing to taxanes. Hence, more research is required to determine whether platinum-based chemotherapy will confer a survival benefit in mCRPC, and the identification of predictive biomarkers and the clinical evaluation of platinum compounds in molecularly selected patients is an urgent but unmet clinical need. The present review focuses on the current status of chemotherapy treatments in mCRPC, interactions with androgen deprivation therapy (ADT) and novel ARSIs, and the main mechanisms of resistance. We will examine the impact of platinum-based treatments in mCRPC and summarize the known predictive biomarkers of platinum response. Finally, future approaches and avenues will be discussed.
Cancer letters. 2021 Sep 10 [Epub ahead of print]
Vicenç Ruiz de Porras, Albert Font, Alvaro Aytes
Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain; Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (BARGO), Badalona, Spain. Electronic address: ., Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (BARGO), Badalona, Spain; Department of Medical Oncology, Catalan Institute of Oncology, Badalona, Spain., Program of Molecular Mechanisms and Experimental Therapeutics in Oncology (ONCOBELL), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Gran Via de L'Hospitalet, Barcelona, Spain; Program Against Cancer Therapeutics Resistance (ProCURE), Catalan Institute of Oncology, Gran Via de L'Hospitalet, Barcelona, Spain. Electronic address: .