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- W4295681809 abstract "ABSTRACTIntroduction Glioblastoma multiforme (GBM) is the deadliest type of brain cancer with poor response to the available therapies, mainly due to intrinsic resistance mechanisms. Chemotherapy is based on alkylating agents, but DNA-repair mechanisms can revert this cytotoxic effect. O6-methylguanine-DNA methyltransferase (MGMT) protein is the primary mechanism for GBM resistance. Therefore, different strategies to suppress its activity have been explored. However, their clinical use has been hindered due to the high toxicity of MGMT inhibitors verified in clinical trials.Areas covered This review article aims to provide the current progress in the development of novel drug delivery systems (DDS) to overcome this resistance. Here, we also review the current knowledge on MGMT-mediated resistance and the clinical outcomes and potential risks of using MGMT inhibitors.Expert opinion To overcome therapeutic limitations, nano-based approaches have been proposed as a suitable solution to improve drug accumulation in the brain tumor tissue and decrease systemic toxicity. DDS to overcome MGMT-mediated resistance in GBM have been mostly developed to deliver MGMT inhibitors and for gene therapy to modulate MGMT gene expression.KEYWORDS: Brain deliverynanomedicinenanoparticlesbrain tumordrug resistanceMGMT gene promoterMGMT protein Article highlights MGMT-mediated resistance limits therapeutic success in GBM patientsConcomitant therapy of alkylating agents and MGMT inhibitors enhance sensitivity to treatmentMGMT inhibitors exacerbate the toxicity of alkylating agents in the healthy tissuesBrain tumor-targeting NPs can reduce systemic toxicity and enhance the therapeutic successFurther development is required to introduce DDS targeting MGMT-resistance to the clinical practiceDeclaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresA reviewer on this manuscript has disclosed receipt of research funding from NIH and is a co-owner for Accelerating Combination Therapies*. Ashvattha Therapeutics Inc. has also licensed one of her patents (*includes equity or options). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper was funded by LA/P/0045/2020 (ALiCE), UIDB/00511/2020 and UIDP/00511/2020 (LEPABE), funded by national funds through FCT/MCTES (PIDDAC); Project 2SMART - engineered Smart materials for Smart citizens, with reference NORTE-01-0145-FEDER-000054, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); FCT supported J.A.L under the Scientific Employment Stimulus - Institutional Call - [CEECINST/00049/2018] and M.J. Ramalho under the Scientific Employment Stimulus - Individual Call – (CEECIND/01741/2021); and Prize Maratona da Saúde for Cancer Research." @default.
- W4295681809 created "2022-09-14" @default.
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- W4295681809 creator A5073105398 @default.
- W4295681809 date "2022-09-20" @default.
- W4295681809 modified "2023-10-17" @default.
- W4295681809 title "Drug delivery in glioblastoma therapy: a review on nanoparticles targeting MGMT-mediated resistance" @default.
- W4295681809 cites W1470598344 @default.
- W4295681809 cites W1786321427 @default.
- W4295681809 cites W1813944011 @default.
- W4295681809 cites W1963675633 @default.
- W4295681809 cites W1965905617 @default.
- W4295681809 cites W1966720603 @default.
- W4295681809 cites W1966743152 @default.
- W4295681809 cites W1985504836 @default.
- W4295681809 cites W2003129478 @default.
- W4295681809 cites W2004432187 @default.
- W4295681809 cites W2008624144 @default.
- W4295681809 cites W2019167849 @default.
- W4295681809 cites W2020693412 @default.
- W4295681809 cites W2022605033 @default.
- W4295681809 cites W2022953178 @default.
- W4295681809 cites W2026064767 @default.
- W4295681809 cites W2036821782 @default.
- W4295681809 cites W2044367685 @default.
- W4295681809 cites W2053123180 @default.
- W4295681809 cites W2063254240 @default.
- W4295681809 cites W2063800774 @default.
- W4295681809 cites W2070909392 @default.
- W4295681809 cites W2071832447 @default.
- W4295681809 cites W2092030031 @default.
- W4295681809 cites W2099431752 @default.
- W4295681809 cites W2100567246 @default.
- W4295681809 cites W2101093124 @default.
- W4295681809 cites W2101364134 @default.
- W4295681809 cites W2101683906 @default.
- W4295681809 cites W2104958914 @default.
- W4295681809 cites W2114858436 @default.
- W4295681809 cites W2121585125 @default.
- W4295681809 cites W2123836229 @default.
- W4295681809 cites W2131565843 @default.
- W4295681809 cites W2134807618 @default.
- W4295681809 cites W2135462171 @default.
- W4295681809 cites W2139835982 @default.
- W4295681809 cites W2146404579 @default.
- W4295681809 cites W2150092048 @default.
- W4295681809 cites W2151230162 @default.
- W4295681809 cites W2164762451 @default.
- W4295681809 cites W2170257720 @default.
- W4295681809 cites W2178761151 @default.
- W4295681809 cites W2179115815 @default.
- W4295681809 cites W2224717864 @default.
- W4295681809 cites W2276773478 @default.
- W4295681809 cites W2322473773 @default.
- W4295681809 cites W2322916630 @default.
- W4295681809 cites W2326103518 @default.
- W4295681809 cites W2332433189 @default.
- W4295681809 cites W2333523065 @default.
- W4295681809 cites W2405475559 @default.
- W4295681809 cites W2480401307 @default.
- W4295681809 cites W2480642725 @default.
- W4295681809 cites W2549628327 @default.
- W4295681809 cites W2549663847 @default.
- W4295681809 cites W2559612585 @default.
- W4295681809 cites W2588760673 @default.
- W4295681809 cites W2591716768 @default.
- W4295681809 cites W2597570800 @default.
- W4295681809 cites W2621590878 @default.
- W4295681809 cites W2765176114 @default.
- W4295681809 cites W2766538795 @default.
- W4295681809 cites W2774441908 @default.
- W4295681809 cites W2774585567 @default.
- W4295681809 cites W2781557781 @default.
- W4295681809 cites W2792626185 @default.
- W4295681809 cites W2800207780 @default.
- W4295681809 cites W2802818037 @default.
- W4295681809 cites W2887355579 @default.
- W4295681809 cites W2888621034 @default.
- W4295681809 cites W2891790331 @default.
- W4295681809 cites W2898331982 @default.
- W4295681809 cites W2898535379 @default.
- W4295681809 cites W2902098035 @default.
- W4295681809 cites W2903849236 @default.
- W4295681809 cites W2913040329 @default.
- W4295681809 cites W2943973500 @default.
- W4295681809 cites W2946698772 @default.
- W4295681809 cites W2967322076 @default.
- W4295681809 cites W2968977249 @default.
- W4295681809 cites W2969256207 @default.
- W4295681809 cites W2977529004 @default.
- W4295681809 cites W2979893646 @default.
- W4295681809 cites W2997516063 @default.
- W4295681809 cites W3010932118 @default.
- W4295681809 cites W3012124816 @default.
- W4295681809 cites W3015905764 @default.