{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:11:34Z","timestamp":1791648694890,"version":"4.3.4"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007059","name":"Internal grant of Palacky University Olomouc","doi-asserted-by":"publisher","award":["IGA_LF_2022_034"],"award-info":[{"award-number":["IGA_LF_2022_034"]}],"id":[{"id":"10.13039\/501100007059","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The lysosomal sequestration of hydrophobic weak-base anticancer drugs is one proposed mechanism for the reduced availability of these drugs at target sites, resulting in a marked decrease in cytotoxicity and consequent resistance. While this subject is receiving increasing emphasis, it is so far only in laboratory experiments. Imatinib is a targeted anticancer drug used to treat chronic myeloid leukaemia (CML), gastrointestinal stromal tumours (GISTs), and a number of other malignancies. Its physicochemical properties make it a typical hydrophobic weak-base drug that accumulates in the lysosomes of tumour cells. Further laboratory studies suggest that this might significantly reduce its antitumor efficacy. However, a detailed analysis of published laboratory studies shows that lysosomal accumulation cannot be considered a clearly proven mechanism of resistance to imatinib. Second, more than 20 years of clinical experience with imatinib has revealed a number of resistance mechanisms, none of which is related to its accumulation in lysosomes. This review focuses on the analysis of salient evidence and raises a fundamental question about the significance of lysosomal sequestration of weak-base drugs in general as a possible resistance mechanism both in clinical and laboratory settings.<\/jats:p>","DOI":"10.3390\/cells12050709","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T05:23:43Z","timestamp":1677129823000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["What Is the Significance of Lysosomal-Mediated Resistance to Imatinib?"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-1248","authenticated-orcid":false,"given":"Petr","family":"Mlejnek","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77515 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/cncr.23651","article-title":"Systemic cancer therapy: Evolution over the last 60 years","volume":"113","author":"Dy","year":"2008","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug resistance in cancer: Role of ATP-dependent transporters","volume":"2","author":"Gottesman","year":"2002","journal-title":"Nat. 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