Zhang Wei, Meng Yan, Liu Na, Wen Xiao-Fei, Yang Tao
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.
Int J Biol Sci. 2015 Aug 1;11(10):1160-70. doi: 10.7150/ijbs.11439. eCollection 2015.
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.
前列腺癌(PCa)仍是西方世界男性中最常见的恶性肿瘤。尽管多年前就已提出通过化学或手术去势进行激素治疗,但迄今为止,这种晚期PCa的主要治疗方法并未从根本上改变。这些治疗反应是暂时的,大多数病例最终会经历PCa复发和转移,甚至由于耐药性的持续发展而进展为去势抵抗性前列腺癌(CRPC)。前列腺癌干细胞(PCSCs)是一小部分细胞,具有无限的自我更新能力,能够再生致瘤后代,在PCa治疗耐药、转移和复发中起重要作用。如今,在对PCSC特性、雄激素受体信号传导和ATP结合盒亚家族G成员2(ABCG2)的作用以及基因组非编码微小RNA和关键信号通路的作用的理解方面取得了进展,这导致了对化疗耐药PCa和CRPC有效的新型疗法的开发。基于这些进展,本综述致力于阐述PCa化疗耐药的机制,揭示关键信号通路之间的相互作用,探索新型生物治疗药物,并阐述化疗耐药PCSCs的功能特性和特定作用,其可能成为抗化疗耐药PCa新型疗法的有希望的靶点。