{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:56:13Z","timestamp":1781672173065,"version":"3.54.5"},"reference-count":128,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Glioblastoma (GBM) remains one of the most aggressive malignancies, characterized by profound heterogeneity and a dismal prognosis. While genomic and transcriptomic profiling have provided structural insights, they often fail to capture the dynamic interactions within the tumor microenvironment (TME). Secretome analysis\u2014the study of proteins actively secreted by tumor cells\u2014offers a functional readout of these interactions and a reservoir for potential biomarkers. In this review, we critically evaluate the role of MALDI-TOF Mass Spectrometry as a strategic tool for GBM secretome profiling. While Liquid Chromatography-Tandem Mass Spectrometry (LC-MS\/MS) remains the gold standard for deep protein discovery, we argue that MALDI-TOF\u2019s speed, cost-effectiveness, and high-throughput capabilities position it as an ideal platform for clinical screening and \u201cspectral phenotyping.\u201d We discuss the technical hurdles, such as ion suppression and the \u201cleakome\u201d (intracellular contamination), and highlight how integrating MALDI with Extracellular Vesicle (EV) enrichment and Artificial Intelligence (AI) can bridge the gap between in vitro discovery and clinical application.<\/jats:p>","DOI":"10.3390\/cimb48060627","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:27:21Z","timestamp":1781666841000},"page":"627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MALDI-TOF Mass Spectrometry for Glioblastoma Secretome Biomarker Screening: A Review of Challenges and Perspectives"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6570","authenticated-orcid":false,"given":"David","family":"Aebisher","sequence":"first","affiliation":[{"name":"Department of Photomedicine and Physical Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6851-5869","authenticated-orcid":false,"given":"Klaudia","family":"Dynarowicz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rostyslav","family":"Marunych","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Rudy","sequence":"additional","affiliation":[{"name":"Student Scientific Club of Biochemists URCell, Faculty of Medicine, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7999-3449","authenticated-orcid":false,"given":"Kacper","family":"Rog\u00f3\u017c","sequence":"additional","affiliation":[{"name":"Student Scientific Club of Biochemists URCell, Faculty of Medicine, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-3809","authenticated-orcid":false,"given":"Aleksandra","family":"Kawczyk-Krupka","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902 Bytom, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ole\u015b","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902 Bytom, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-5464","authenticated-orcid":false,"given":"Dorota","family":"Bartusik-Aebisher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzesz\u00f3w, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11246","DOI":"10.1021\/acs.analchem.5c07924","article-title":"Single-Cell Metabolic Profiling in a Glioblastoma Coculture Model Using AP-MALDI-Based Mass Spectrometry Imaging","volume":"98","author":"Kontrimaite","year":"2026","journal-title":"Anal. 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