Overcoming drug resistance in castrate-resistant prostate cancer: current mechanisms and emerging therapeutic approaches DOI Open Access
Adam Khorasanchi, Feng Hong, Yuanquan Yang

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Metastatic castration-resistant prostate cancer (mCRPC) is driven by a complex network of resistance mechanisms against standard-of-care therapies, resulting in poor long-term outcomes. This review offers uniquely comprehensive and integrative perspective on these pathways, systematically examining both androgen receptor (AR)-dependent factors (including AR overexpression, point mutations, glucocorticoid signaling, splice variants, post-translational modifications, altered coregulators, intratumoral hormone biosynthesis) AR-independent pathways (such as neuroendocrine differentiation, lineage plasticity, alternative growth factor signaling). We also highlight influencing immunotherapy, chemotherapy, radiopharmaceutical therapy targeted therapy. By synthesizing emerging insights across domains, this not only clarifies the underlying biology mCRPC but identifies key leverage points for more effective interventions. Building foundation, we propose forward-looking framework overcoming drug resistance, emphasizing importance biomarker-guided patient selection, combination strategies that simultaneously target multiple mechanisms, novel therapies under investigation. These recommendations are intended to guide future clinical trial designs research priorities move beyond incremental improvements. Ultimately, synthesis aims serve resource clinicians researchers accelerate development durable, precision-based treatment mCRPC.

Language: Английский

Overcoming drug resistance in castrate-resistant prostate cancer: current mechanisms and emerging therapeutic approaches DOI Open Access
Adam Khorasanchi, Feng Hong, Yuanquan Yang

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Metastatic castration-resistant prostate cancer (mCRPC) is driven by a complex network of resistance mechanisms against standard-of-care therapies, resulting in poor long-term outcomes. This review offers uniquely comprehensive and integrative perspective on these pathways, systematically examining both androgen receptor (AR)-dependent factors (including AR overexpression, point mutations, glucocorticoid signaling, splice variants, post-translational modifications, altered coregulators, intratumoral hormone biosynthesis) AR-independent pathways (such as neuroendocrine differentiation, lineage plasticity, alternative growth factor signaling). We also highlight influencing immunotherapy, chemotherapy, radiopharmaceutical therapy targeted therapy. By synthesizing emerging insights across domains, this not only clarifies the underlying biology mCRPC but identifies key leverage points for more effective interventions. Building foundation, we propose forward-looking framework overcoming drug resistance, emphasizing importance biomarker-guided patient selection, combination strategies that simultaneously target multiple mechanisms, novel therapies under investigation. These recommendations are intended to guide future clinical trial designs research priorities move beyond incremental improvements. Ultimately, synthesis aims serve resource clinicians researchers accelerate development durable, precision-based treatment mCRPC.

Language: Английский

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