{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:02:22Z","timestamp":1790326942445,"version":"4.1.0"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Lysosomes are critical cellular organelles that not only regulate metabolic regulation but also play pivotal roles in cell death, signal transduction, and tumorigenesis. The various ion channels expressed on the lysosomal membrane are central to these physiological functions; they intricately maintain lysosomal pH homeostasis, calcium ion homeostasis, and membrane potential. Consequently, the dysregulation of these channels has emerged as a potential target of tumor cells, driving tumor cell proliferation, metastasis, apoptosis, and drug resistance. This review summarizes the structure and function of major lysosomal ion channels, emphasizing their central roles in regulating the tumor microenvironment, cell survival, and treatment resistance. Specifically, we highlight their involvement in mediating resistance to chemotherapy, radiotherapy, and immunotherapy, elucidating the associated molecular mechanisms. Furthermore, we explore the prospects and challenges of developing targeted therapeutic strategies towards these ion channels to overcome tumor drug resistance.<\/jats:p>","DOI":"10.3389\/fphar.2026.1911117","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:12:16Z","timestamp":1790323936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting lysosomal ion channels to overcome cancer treatment resistance: emerging mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Na","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Intelligent Oncology for Breast Cancer, Center for Intelligent Oncology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Center for Tumor Therapy, The Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Deng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Intelligent Oncology for Breast Cancer, Center for Intelligent Oncology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10008","DOI":"10.1038\/s41467-024-54324-9","article-title":"Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3\u03b2\/\u03b2-Catenin\/MITF-axis","volume":"15","author":"Abrahamian","year":"2024","journal-title":"Nat. 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