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Ion channels and extrachromosomal DNA (ecDNA) have emerged as key drivers of such adaptive processes by influencing signaling, metabolism, and immune interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010cell RNA\u2010sequencing (scRNA\u2010seq) datasets (primary PCa and castration\u2010resistant PCa) to determine ion channel and transporter expression profiles in tumor and stromal cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis showed cell type\u2013specific 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\u2010resistant clones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2014through ion channel modulators, ferroptosis induction, and ecDNA\u2010targeting interventions (BET\/HDAC inhibitors, CRISPR\u2010based methods) offers a promising way to overcome resistance. Integration of multi\u2010omics, and combination treatments will be key to construct precision medicine strategies and improve clinical outcomes in advanced PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70139","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T20:54:00Z","timestamp":1770152040000},"page":"619-636","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Happening in the Prostate Tumor Microenvironment: Ion Channels and Extrachromosomal DNA Driving Phenotypic Plasticity"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1868-6712","authenticated-orcid":false,"given":"Sara","family":"Darbandi","sequence":"first","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Urbanucci","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research Oslo University Hospital Oslo Norway"},{"name":"Center for Cancer Eradication Research, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre Finland Tampere University Tampere Finland"},{"name":"Finnish Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sini","family":"Hakkola","sequence":"additional","affiliation":[{"name":"Center for Cancer Eradication Research, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre Finland Tampere University Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanita","family":"Gujral","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Darbandi","sequence":"additional","affiliation":[{"name":"Department of Oncological Sciences Tisch Cancer Institute New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6879-6058","authenticated-orcid":false,"given":"Ahmed","family":"Eraky","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goutam","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Tewari","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Kyprianou","sequence":"additional","affiliation":[{"name":"Department of Urology Icahn School of Medicine at Mount Sinai New York USA"},{"name":"Department of Oncological Sciences Tisch Cancer Institute New York USA"},{"name":"Department of Pathology &amp; Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911440"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706450"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01035"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802905"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611310"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-96-2763-9_13"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jfas.2021.08.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02404"},{"key":"e_1_2_9_10_1","first-page":"3195","article-title":"Phase I Trial of a First\u2010in\u2010Class ATR Inhibitor VX\u2010970 as Monotherapy (Mono) or in Combination (Combo) With Carboplatin (Cp) Incorporating Pharmacodynamics (PD) Studies","volume":"38","author":"O'Carrigan B.","year":"2016","journal-title":"American Society of Clinical Oncology"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.305.3.319"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01406-w"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01405-x"},{"key":"e_1_2_9_14_1","unstructured":"\u4f50\u85e4\u88d5\u771f. 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