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Enzalutamide (Enz) is a next-generation androgen receptor (AR) antagonist used to treat castration-resistant prostate cancer (CRPC). Unfortunately, the relapsing nature of CRPC results in the development of Enz resistance in many patients. Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins, which include microRNAs (miRNA), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs with known and unknown functions. Recently, dysregulation of ncRNAs in CRPC, particularly their regulatory function in drug resistance, has attracted more and more attention. Herein, we introduce the roles of dysregulation of different ncRNAs subclasses in the development of CRPC progression and Enz resistance. Recently determined mechanisms of Enz resistance are discussed, focusing mainly on the role of AR-splice variant-7 (AR-V7), mutations, circRNAs and lncRNAs that act as miRNA sponges. Also, the contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are discussed. We summarize the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and highlight the prospect of future therapeutic strategies against Enz resistance.
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http://dx.doi.org/10.1016/j.canlet.2023.216247 | DOI Listing |
Adv Sci (Weinh)
September 2025
Department of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China.
Despite the expanding clinical application of second-generation anti-androgens like enzalutamide (ENZ) in hormone-sensitive prostate cancer (HSPC), therapeutic resistance culminating in castration-resistant prostate cancer (CRPC) persists as an unresolved clinical crisis. Through comprehensive single-cell transcriptomic profiling of ENZ-naïve and ENZ-treated tumors, an expansion of ENZ-resistant myofibroblastic cancer-associated fibroblast (designated STEAP4 myoCAF) is identified that correlates with adverse clinical outcomes. Strikingly, STEAP4 myoCAF demonstrated intrinsic ENZ resistance through a mechanistically novel pathway involving transcription factor binding to IGHM enhancer 3 (TFE3)-mediated autophagy activation.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico.
Advanced prostate cancer frequently develops resistance to antiandrogen therapy and acquires an aggressive neuroendocrine phenotype. Antiandrogens stimulate peroxisome proliferator-activated receptor gamma (PPARG) signaling and cancer progression. Molecular iodine (I) induces cytotoxic effects in prostate cancer cell lines and antineoplastic effects in neuroblastoma and breast cancer through the indirect activation of PPARG.
View Article and Find Full Text PDFTheranostics
August 2025
School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China.
Enzalutamide (Enz) is the first-line therapy for castration-resistant prostate cancer (CRPC). However, drug resistance has hindered its further application. Moreover, CRPC is frequently prone to metastasis, particularly to bone (BmCRPC).
View Article and Find Full Text PDFBiomark Res
August 2025
Department of Urology, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, People's Republic of China.
The androgen receptor signaling inhibitor enzalutamide (Enz) is one the primary therapeutic drugs for advanced prostate cancer (PCa). Nevertheless, most of patients ultimately develop resistance to Enz. Through an integrated analysis of CRISPR genome-wide and kinome-wide screens, coupled with observations of elevated expression levels in Enz-resistant cell lines and PCa tumor tissues, our study identified RPS6KC1 as a novel essential gene implicated in Enz resistance.
View Article and Find Full Text PDFSmall
August 2025
Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education), Shandong University, Jinan, 250061, China.
Metacomposites can achieve epsilon-negative (ɛ' <0, EN) and epsilon-near-zero (ɛ' ≈ 0, ENZ) responses below the GHz band, thus providing a brand-new design principle for developing meta-structure electronic components. However, its negative response presently cannot fully cover the kHz-MHz band and is thus constrained by an unclear regulation mechanism. This study offers a corncob-derived carbon/polyaniline (CC/PANI) metacomposite featuring a bicontinuous bilayer architecture to match the electromagnetic response in the frequency band of 10 kHz-45 MHz.
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