1. Department of Pharmacology, School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
2. Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
3. Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
4. Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
# These two authors contributed equally to this work.
Prostate cancer (PCa) remains the most prevalent malignancy among males in the western world. Though hormonal therapies through chemical or surgical castration have been proposed many years ago, heretofore, such mainstay for the treatment on advanced PCa has not fundamentally changed. These therapeutic responses are temporary and most cases will eventually undergo PCa recurrence and metastasis, or even progress to castration-resistant prostate cancer (CRPC) due to persistent development of drug resistance. Prostate cancer stem cells (PCSCs) are a small population of cells, which possess unlimited self-renewal capacities, and can regenerate tumorigenic progenies, and play an essential role in PCa therapy resistance, metastasis and recurrence. Nowadays advanced progresses have been made in understanding of PCSC properties, roles of androgen receptor signaling and ATP-binding cassette sub-family G member 2 (ABCG2), as well as roles of genomic non-coding microRNAs and key signaling pathways, which have led to the development of novel therapies which are active against chemoresistant PCa and CRPC. Based on these progresses, this review is dedicated to address mechanisms underlying PCa chemoresistance, unveil crosstalks among pivotal signaling pathways, explore novel biotherapeutic agents, and elaborate functional properties and specific roles of chemoresistant PCSCs, which may act as a promising target for novel therapies against chemoresistant PCa.
Keywords: prostate cancer, chemoresistance, cancer stem cell, androgen receptor, cancer recurrence