{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:46:09Z","timestamp":1782794769235,"version":"3.54.5"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) exhibits marked resistance to radiotherapy due to hypoxia, metabolic adaptation, enhanced DNA damage response, and the persistence of glioma stem cells (GSCs). Radiosensitisers have therefore become a key therapeutic focus, yet clinically effective agents remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This narrative review synthesises current knowledge on GBM radioresistance mechanisms and evaluates prodigiosin (PG)\u2013a marine-derived tripyrrole pigment\u2013as a potential radiosensitiser, based on its diverse antitumour mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Content<\/jats:title>\n                    <jats:p>\n                      PG demonstrates multifaceted cytotoxic activity in GBM through cytosolic acidification, mitochondrial destabilisation, ER stress and autophagy-associated cell death, DNA intercalation and copper-dependent oxidative cleavage, modulation of MAPK and PI3K\u2013Akt signalling, and inhibition of proliferative and survival pathways. These actions intersect with major determinants of radioresistance, including DNA repair efficiency, ROS adaptation, GSC maintenance and checkpoint recovery. We outline mechanistic hypotheses for PG\u2013radiation synergy, discuss delivery challenges such as BBB penetration, and propose a structured roadmap for\n                      <jats:italic>in vitro<\/jats:italic>\n                      ,\n                      <jats:italic>in vivo<\/jats:italic>\n                      and translational investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although no studies have directly evaluated PG in combination with radiation, its biological profile supports strong theoretical potential as a radiosensitiser. This review integrates current evidence into a mechanistic pharmacology framework and outlines a structured experimental roadmap for evaluating prodigiosin as a marine-derived radiosensitiser in preclinical drug discovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1767203","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:24:48Z","timestamp":1782793488000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prodigiosin in glioblastoma: mechanistic pharmacology and rationale for its development as a radiosensitiser"],"prefix":"10.3389","volume":"17","author":[{"given":"Hansika","family":"Ray","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/s0140-6736(76)91285-x","article-title":"Hypoxic cell sensitisers in radiotherapy","volume":"1","author":"Adams","year":"1976","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"vdac160","DOI":"10.1093\/noajnl\/vdac156","article-title":"Factors affecting the radiation response in glioblastoma","volume":"4","author":"Aiyappa-Maudsley","year":"2022","journal-title":"Neurooncol Adv."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.3390\/cancers12092511","article-title":"Radioresistance in glioblastoma and the development of radiosensitizers","volume":"12","author":"Ali","year":"2020","journal-title":"Cancers"},{"key":"B4","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/s12935-022-02815-4","article-title":"Rise of the natural red pigment \u201cprodigiosin\u201d as an immunomodulator in cancer","volume":"22","author":"Anwar","year":"2022","journal-title":"Cancer Cell Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"14706","DOI":"10.1038\/s41598-020-71157-w","article-title":"Prodigiosin\/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights","volume":"10","author":"Anwar","year":"2020","journal-title":"Sci. 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