Happening in the Prostate Tumor Microenvironment: Ion Channels and Extrachromosomal DNA Driving Phenotypic Plasticity.
2/5 보강
TL;DR
The combinatorial approach of CDKi and PARPi, through multi-dimensional mechanistic integration, holds strong potential as a key strategy to overcome PARPi resistance and expand the population of patients who can benefit from this class of therapies.
OpenAlex 토픽 ·
Ferroptosis and cancer prognosis
Cancer Cells and Metastasis
Cancer, Stress, Anesthesia, and Immune Response
The combinatorial approach of CDKi and PARPi, through multi-dimensional mechanistic integration, holds strong potential as a key strategy to overcome PARPi resistance and expand the population of pati
APA
Sara Darbandi, Alfonso Urbanucci, et al. (2026). Happening in the Prostate Tumor Microenvironment: Ion Channels and Extrachromosomal DNA Driving Phenotypic Plasticity.. The Prostate, 86(6), 619-636. https://doi.org/10.1002/pros.70139
MLA
Sara Darbandi, et al.. "Happening in the Prostate Tumor Microenvironment: Ion Channels and Extrachromosomal DNA Driving Phenotypic Plasticity.." The Prostate, vol. 86, no. 6, 2026, pp. 619-636.
PMID
41632930
Abstract
[BACKGROUND] Plasticity of cancer, including epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) self-renewal, and microenvironmental adaptation, drives metastasis, therapy resistance, and poor outcomes in prostate cancer (PCa). Ion channels and extrachromosomal DNA (ecDNA) have emerged as key drivers of such adaptive processes by influencing signaling, metabolism, and immune interactions.
[METHODS] We evaluated available evidence on ion channel biology, ecDNA dynamics, and their roles in tumor plasticity and drug resistance in PCa. Further, we analyzed two publicly accessible single-cell RNA-sequencing (scRNA-seq) datasets (primary PCa and castration-resistant PCa) to determine ion channel and transporter expression profiles in tumor and stromal cell populations.
[RESULTS] Our analysis showed cell type-specific expression of many ion channels, including KCNJ10, CACNA1H, and CLIC1, and identification of six transporters (SLC25A1, SLC25A10, SLC25A33, SLC25A42, SLC29A2, SLC7A11) strongly enriched in luminal tumor cells. The discovered genes regulate mitochondrial metabolism, redox homeostasis, nucleotide biosynthesis, immune modulation, and resistance to ferroptosis, all contributing to tumor growth. ecDNA facilitates oncogene amplification (e.g., MYC, EGFR), induction of EMT, and immune evasion, driving intratumoral heterogeneity and therapy-resistant clones.
[CONCLUSIONS] Ion channels and ecDNA are central to the disease progression and treatment resistance of PCa through regulation of EMT, CSC phenotype, and tumor microenvironment (TME) interactions. Targeting the drivers-through ion channel modulators, ferroptosis induction, and ecDNA-targeting interventions (BET/HDAC inhibitors, CRISPR-based methods) offers a promising way to overcome resistance. Integration of multi-omics, and combination treatments will be key to construct precision medicine strategies and improve clinical outcomes in advanced PCa.
[METHODS] We evaluated available evidence on ion channel biology, ecDNA dynamics, and their roles in tumor plasticity and drug resistance in PCa. Further, we analyzed two publicly accessible single-cell RNA-sequencing (scRNA-seq) datasets (primary PCa and castration-resistant PCa) to determine ion channel and transporter expression profiles in tumor and stromal cell populations.
[RESULTS] Our analysis showed cell type-specific expression of many ion channels, including KCNJ10, CACNA1H, and CLIC1, and identification of six transporters (SLC25A1, SLC25A10, SLC25A33, SLC25A42, SLC29A2, SLC7A11) strongly enriched in luminal tumor cells. The discovered genes regulate mitochondrial metabolism, redox homeostasis, nucleotide biosynthesis, immune modulation, and resistance to ferroptosis, all contributing to tumor growth. ecDNA facilitates oncogene amplification (e.g., MYC, EGFR), induction of EMT, and immune evasion, driving intratumoral heterogeneity and therapy-resistant clones.
[CONCLUSIONS] Ion channels and ecDNA are central to the disease progression and treatment resistance of PCa through regulation of EMT, CSC phenotype, and tumor microenvironment (TME) interactions. Targeting the drivers-through ion channel modulators, ferroptosis induction, and ecDNA-targeting interventions (BET/HDAC inhibitors, CRISPR-based methods) offers a promising way to overcome resistance. Integration of multi-omics, and combination treatments will be key to construct precision medicine strategies and improve clinical outcomes in advanced PCa.
🏷️ 키워드 / MeSH
- Humans
- Tumor Microenvironment
- Male
- Ion Channels
- Prostatic Neoplasms
- Epithelial-Mesenchymal Transition
- Neoplastic Stem Cells
- Drug Resistance
- Neoplasm
- DNA
- Phenotype
- Epithelial‐Mesenchymal Transition (EMT)
- Mesenchymal‐Epithelial Transition (MET)
- Metastasis
- Microenvironment
- Phenotypic Landscape
- Prostate Cancer
- Therapeutic Targeting
- Tumor Recurrence