Abstract
Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.
Highlights
Given the crucial roles of inflammatory signaling in castration-resistant prostate cancer (CRPC) development, more and more targeted therapeutic strategies have emerged to interrupt inflammatory signaling in Prostate cancer (PCa) cells and in the tumor microenvironment (TME)
Tumor-associated immune/inflammatory cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), constitute an immunosuppressive TME that helps and accommodates cancer cells escaping from immune surveillance and produces pro-inflammatory cytokines, chemokines, and growth factors to promote tumor growth and progression and to counter any stress and insult conditions, such as chemo/radiotherapy and androgen deprivation therapy (ADT)
These findings suggest that the expansion of B-cell populations by castration is involved in promoting CRPC development; in localized PCa, increased plasma cells are associated with improved outcomes [61,63,70,71,72]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. We and many others have reported that immune/inflammatory signaling in both cancer cells and the tumor microenvironment (TME) plays important roles in CRPC growth and development [13,14,15,16,17]. Inflammatory signaling activation has been found in almost all cancers and is associated with cell transformation, tumorigenesis, tumor progression, and therapy resistance [14,15,16]. Given the crucial roles of inflammatory signaling in CRPC development, more and more targeted therapeutic strategies have emerged to interrupt inflammatory signaling in PCa cells and in the TME. We briefly review the recent advances in the roles of inflammatory signaling in the emergence and maintenance of CRPC as well as the therapeutic strategies that target inflammatory signaling for the treatment of PCa castration resistance
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