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ABCB1 (P-glycoprotein) and ABCG2 (BCRP) are overexpressed in brain tumors, including gliomas. Co-existing transporters can undermine inhibition of either target, especially when both export the same drug. Clinical translation of ABC transporter inhibition remains debated, and effective inhibitors are not yet approved, with trials reporting limited efficacy and notable toxicities.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/revisiting-strategies-to-target-abc-transporter-mediated-drug-resistance-in-cns-cancer/369953/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/revisiting-strategies-to-target-abc-transporter-mediated-drug-resistance-in-cns-cancer/369953.png","ImageObject",300,407,{"name":92,"@type":93},"Guten tag","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why do many anticancer drugs fail to treat brain tumors?","Question",{"text":112,"@type":113},"Drug effectiveness is reduced by the blood-brain barrier and by overexpression of ATP-binding cassette (ABC) transporters that decrease drug penetration into the CNS and tumors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which two ABC transporters are highlighted as overexpressed in brain tumors?",{"text":117,"@type":113},"ABCB1, known as P-glycoprotein (P-gp), and ABCG2, known as breast cancer resistance protein (BCRP), are both described as overexpressed in brain tumors including gliomas.",{"name":119,"@type":110,"acceptedAnswer":120},"Why can inhibiting one ABC transporter be insufficient?",{"text":121,"@type":113},"If multiple ABC transporters are present, inhibiting only one may not restore efficacy, particularly when both transport the same anticancer drug and continue to export it.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},369953,1790318476,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},687212321768,"https://ap-avatar.wpscdn.com/avatar/a0010bdbe886d2fe77?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789897067658708522","Cancer Biol Med 2025. doi: 10.20892/j.issn.2095-3941.2025.0060  \nREVIEW  \nRevisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer  \nHaneen Amawi1, Alaa M. Hammad2, F. Scott Hall3, Noor Hussein4, Aseel O. Rataan1, Abeer Mrayyan5, Taqwa Al-kofahi5, Ali Hmedat6, Charles R. Ashby Jr.7, Amit K. Tiwari8  \n1 Department of Clinical Pharmacy and Pharmacy Practice, College of Pharmacy, Yarmouk University, Irbid 21163, Jordan;  \n2 Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan; 3 Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA; 4 Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA 94305, USA; 5 Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 21163, Jordan; 6 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan; 7 Department of Pharmaceutical Sciences, College of Pharmacy, St. John’s University, Queens, NY 11439, USA; 8 Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA  \n\n| ABSTRACT | A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex bloodbrain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, particularly if both transport the same anticancer drug. The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs. However, the clinical relevance as a therapeutic target in human tumors remains a matter of contention. Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance, none are currently approved. Furthermore, the ABC |\n| --- | --- |\n| KEYWORDS | transporter inhibitors in clinical trials produced low or no clinical efficacy, significant toxicities, and unsuitable pharmacokinetic profiles. Therefore, innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance. This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments. The molecular alterations in BBB following brain tumor development, which are linked to various cancer therapies, are discussed. The overexpression of ABCB1 and ABCG2 at the BBB is discussed, potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed, and the implementation of novel approaches is considered.\u003Cbr>ABC transporters; MDR; ABCG2; ABCB1; Brain Tumors; BBB |\n\nIntroduction  \nATP-binding cassette (ABC) transporters are among the most diverse protein superfamilies in humans 1,2 . These ABC  \nCorrespondence to: Haneen Amawi and Amit K. Tiwari  \nE-mail: [haneen.amawi@yu.edu.jo and](haneen.amawi@yu.edu.jo and) [atiwari@uams.edu](atiwari@uams.edu)  \nORCID ID: [https://orcid.org/0000-0002-1009-9169](https://orcid.org/0000-0002-1009-9169) and  \n[https://orcid.org/0000-0002-0275-0724](https://orcid.org/0000-0002-0275-0724)  \nReceived February 8, 2025; accepted May 7, 2025;  \npublished online September 29, 2025. Available [at www.cancerbiomed.org](at www.cancerbiomed.org)  \n©2025 The Authors. Creative Commons Attribution-NonCommercial 4.0 International License  \ntransporters are structurally unique, ATP-dependent, andefflux a wide rang","cbCaicLhpzFq7BP5","https://ap.wps.com/l/cbCaicLhpzFq7BP5","pdf",3171864,23,"English","# Introduction\n# ABC transporter structure and diversity\n# ABC transporters in drug absorption, distribution, and elimination\n# ABC transporters at the blood-brain barrier and drug resistance\n# Clinical relevance of ABC transporter inhibitors\n# Strategies and challenges for therapeutic targeting","[{\"question\":\"Why do many anticancer drugs fail to treat brain tumors?\",\"answer\":\"Drug effectiveness is reduced by the blood-brain barrier and by overexpression of ATP-binding cassette (ABC) transporters that decrease drug penetration into the CNS and tumors.\"},{\"question\":\"Which two ABC transporters are highlighted as overexpressed in brain tumors?\",\"answer\":\"ABCB1, known as P-glycoprotein (P-gp), and ABCG2, known as breast cancer resistance protein (BCRP), are both described as overexpressed in brain tumors including gliomas.\"},{\"question\":\"Why can inhibiting one ABC transporter be insufficient?\",\"answer\":\"If multiple ABC transporters are present, inhibiting only one may not restore efficacy, particularly when both transport the same anticancer drug and continue to export it.\"}]","Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer | PDF",1790185376,58]