Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer

Abstract

Prostate cancer (PCa) is responsible for significant cancer-related morbidity and mortality following local treatment failure in men. The initial stages of PCa are typically managed with a combination of surgical resection and/or androgen deprivation therapy (ADT). Unfortunately, a significant proportion of PCa continues to progress despite being at castrate levels of testosterone (<50 ng/dl), at which point it is coined castration-resistant prostate cancer (CRPC). In recent years, many novel therapeutics and drug combinations have been created for CRPC patients. These include immune checkpoint inhibitors, chemokine receptor antagonists, steroidogenic enzyme inhibition, and novel tyrosine kinase inhibitors as well as combinations of drugs. The selection of the most appropriate therapy depends on several factors like stage of the disease, age of the patient, metastasis, functional status, and response towards previous therapies. Here, we review the current state of the literature regarding treatment modalities, focusing on the treatment recommendations per the American Urological Association (AUA), recent clinical trials, and their limitations. An accurate and reliable overview of the strengths and limitations of PCa therapeutics could also allow personalized therapeutic interventions against PCa.

Keywords: Androgen deprivation therapy; Asymptomatic mCRPC; CRPC; CRPC treatment; Chemokine receptor antagonists; Immune checkpoint inhibitors; Immunotherapy; NM-CRPC; Prostate cancer; Secondary hormonal manipulations; Steroidogenic enzyme inhibition; Symptomatic mCRPC; Tumor microenvironment; Tumor-associated macrophages; Tyrosine kinase inhibitors.