Deregulated miRNAs in enzalutamide resistant prostate cancer: A comprehensive review of key molecular alterations and clinical outcomes

Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related deaths in male population worldwide. Since the growth and progression of PC highly depend on the androgen pathway, androgen deprivation therapy (ADT) is the mainstay of systemic treatment. Enzalutamide is a second-generation antiandrogen, which is widely used for the treatment of advanced and metastatic PC. However, treatment failure and disease progression, caused by the emergence of enzalutamide resistant phenotypes, remains an important clinical challenge. MicroRNAs (miRNAs) are key regulators of gene expression and have recently emerged as potential biomarkers for being stable and easily analysed in several biological fluids. Several miRNAs that exhibit dysregulated expression patterns in enzalutamide-resistant PC have recently been identified, including miRNAs that modulate critical signalling pathways and genes involved in PC growth, survival and in the acquisition of enzalutamide phenotype. The understanding of molecular mechanisms by which miRNAs promote the development of enzalutamide resistance can provide valuable insights into the complex interplay between miRNAs, gene regulation, and treatment response in PC. Moreover, these miRNAs could serve as valuable tools for monitoring treatment response and disease progression during enzalutamide administration. This review summarises the miRNAs associated with enzalutamide resistance in PC already described in the literature, focusing on their biological roles and on their potential as biomarkers.