{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:54:53Z","timestamp":1791748493926,"version":"4.3.4"},"reference-count":164,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Research Chairs Initiative","award":["98337"],"award-info":[{"award-number":["98337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers (PSs) selectively. The reactive oxygen species (ROS), which kill cells, are released by these PSs when they are stimulated by light. According to recent developments in PDT, its efficacy may go beyond traditional tumor cells, providing a viable remedy for the resistance shown by CSCs. Researchers want to improve the targeted elimination and selective targeting of CSCs by combining PDT with new PSs and customized delivery systems. Studies emphasize how PDT affects CSCs as well as bulk tumor cells. According to studies, PDT not only limits CSC growth but also modifies their microenvironment, which lowers the possibility of recovery. Additionally, studies are being conducted on the utilization of PDT and immunotherapeutic techniques to improve treatment efficacy and overcome inherent resistance of CSCs. In conclusion, PDT is a viable strategy for treating carcinogenesis driven by CSCs. By applying the most recent advancements in PDT technologies and recognizing how it interacts with CSCs, this treatment has the potential to surpass traditional resistance mechanisms and improve the future of cancer patients. Clinical and preclinical studies highlight that combining PDT with CSC-targeted approaches has the potential to overcome current therapy limitations. Future efforts should focus on clinical validation, optimizing light delivery and PS use, and developing effective combination strategies to target CSCs.<\/jats:p>","DOI":"10.3390\/pharmaceutics17050559","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:18:02Z","timestamp":1745475482000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0793-4300","authenticated-orcid":false,"given":"Sheeja S.","family":"Rajan","sequence":"first","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P. Jose","family":"Merlin","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-827X","authenticated-orcid":false,"given":"Heidi","family":"Abrahamse","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, P.O. Box 17011, Johannesburg 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5637","DOI":"10.2147\/IJN.S461300","article-title":"Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review","volume":"19","author":"Dilenko","year":"2024","journal-title":"Int. J. 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