{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:48:33Z","timestamp":1789213713929,"version":"build-2803163510"},"reference-count":173,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Direcci\u00f3n General de Pol\u00edticas de Investigaci\u00f3n en Salud","award":["FPIS2024-HIM-4144"],"award-info":[{"award-number":["FPIS2024-HIM-4144"]}]},{"name":"Direcci\u00f3n General de Pol\u00edticas de Investigaci\u00f3n en Salud","award":["HIM\/2023\/036"],"award-info":[{"award-number":["HIM\/2023\/036"]}]},{"name":"Hospital Infantil de M\u00e9xico Federico G\u00f3mez","award":["FPIS2024-HIM-4144"],"award-info":[{"award-number":["FPIS2024-HIM-4144"]}]},{"name":"Hospital Infantil de M\u00e9xico Federico G\u00f3mez","award":["HIM\/2023\/036"],"award-info":[{"award-number":["HIM\/2023\/036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>P-glycoprotein (P-gp), a transmembrane efflux pump encoded by the ABCB1\/MDR1 gene, is a major contributor to multidrug resistance in hematological malignancies. These malignancies, arising from hematopoietic precursors at various differentiation stages, can manifest in the bone marrow, circulate in the bloodstream, or infiltrate tissues. P-gp overexpression in malignant cells reduces the efficacy of chemotherapeutic agents by actively expelling them, decreasing intracellular drug concentrations, and promoting multidrug resistance, a significant obstacle to successful treatment. This review examines recent advances in combating P-gp-mediated resistance, including the development of novel P-gp inhibitors, innovative drug delivery systems (e.g., nanoparticle-based delivery), and strategies to modulate P-gp expression or activity. These modulation strategies encompass targeting relevant signaling pathways (e.g., NF-\u03baB, PI3K\/Akt) and exploring drug repurposing. While progress has been made, overcoming P-gp-mediated resistance remains crucial for improving patient outcomes. Future research directions should prioritize the development of potent, selective, and safe P-gp inhibitors with minimal off-target effects, alongside exploring synergistic combination therapies with existing chemotherapeutics or novel agents to effectively circumvent multidrug resistance in hematological malignancies.<\/jats:p>","DOI":"10.3390\/ijms26104701","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:27:41Z","timestamp":1747218461000},"page":"4701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome"],"prefix":"10.3390","volume":"26","author":[{"given":"Pablo","family":"\u00c1lvarez-Carrasco","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Inmunolog\u00eda y Prote\u00f3mica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"},{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Morales-Villamil","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Inmunolog\u00eda y Prote\u00f3mica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"},{"name":"Facultad de Medicina, Benem\u00e9rita Universidad de Puebla, Puebla 72000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-2888","authenticated-orcid":false,"given":"Carmen","family":"Maldonado-Bernal","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Inmunolog\u00eda y Prote\u00f3mica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nanayakkara, A.K., Follit, C.A., Chen, G., Williams, N.S., Vogel, P.D., and Wise, J.G. 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