Ask about this productRelated genes to: MGMT protein
- Gene:
- MGMT NIH gene
- Name:
- O-6-methylguanine-DNA methyltransferase
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 10q26.3
- Locus Type:
- gene with protein product
- Date approved:
- 1989-10-16
- Date modifiied:
- 2016-10-05
Related products to: MGMT protein
Related articles to: MGMT protein
- Glioblastoma (GBM) remains incurable due to the blood-brain barrier (BBB) limiting drug delivery and intrinsic/acquired resistance to temozolomide (TMZ), the first-line chemotherapy. Here, we developed Angiopep-2 (Ang)-modified natural killer cell-derived extracellular vesicles (Ang-NK-EV) for targeted TMZ delivery (Ang-NK-EV@TMZ) to address these bottlenecks. NK-EV were prepared via freeze-thaw extrusion of NK-92 cells, loaded with TMZ, and surface-functionalized with Ang to target LRP1 (highly expressed at the BBB and on GBM cells). Characterization confirmed Ang-NK-EV@TMZ exhibited spherical morphology, preserved EV markers (TSG101, CD9/63/81), and retained NK cell-derived immune factors (IFN-γ, GZMB). In vitro, Ang modification enhanced GBM cell uptake (2.5-3.2-fold vs. NK-EV) and BBB transcytosis (2.8-3.5-fold vs. free TMZ). Ang-NK-EV@TMZ reversed TMZ resistance by modulating STING/ mTOR/ MGMT signaling (via IFN-γ) and inducing apoptosis (elevated cleaved caspase-3, γ-H2AX). It also triggered immunogenic cell death (increased ATP, HMGB1) and polarized macrophages to M1-like phenotypes. In orthotropic GBM models, Ang-NK-EV@TMZ accumulated in brain tumors, inhibited growth (7.2-fold lower bioluminescence vs. PBS), and extended median survival (42 days vs. 18 days for PBS). No significant organ toxicity or hemolysis was observed. This platform integrates targeted chemotherapy and immune modulation, highlighting NK-EV' potential for GBM therapy. - Source: PubMed
Publication date: 2026/04/25
Liu JunWei WenjinHuang QianliangGong YingGuo BangmingZhang ZheYang YancongXue ShuaishuaiCai YonghuaZhan ZhengmingLi PengJiang QiuhuaYe XinyunSong YeGuo Hua - Microsatellite-stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI). The MAYA trial used temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesizing that TMZ-induced hypermutation could sensitize tumors to ICI; the primary endpoint was met, showing durable responses with TMZ plus ipilimumab and nivolumab. We perform integrated spatial, transcriptomic, and immune profiling of longitudinal tumor and blood samples from patients treated on the MAYA trial. Post-TMZ increases in tumor mutational burden associate with improved progression-free survival. Spatial profiling demonstrates that clinical benefit is greatest in permissive tumor microenvironments. Responders exhibit enrichment of cytotoxic T cells across tumor and stromal compartments, whereas non-responders display heterogeneous cellular neighborhoods, with fibroblasts in close spatial proximity to T cells, consistent with barriers to immune-mediated clearance. Longitudinal peripheral immune profiling shows that early upregulation of TIGIT and PD-1 following TMZ exposure predicts resistance. Together, these findings indicate that both mutational evolution and spatial immune architecture contribute to immune sensitization in MGMT-silenced MSS CRC. Clinical Trial Identification: NCT03832621. - Source: PubMed
Publication date: 2026/04/25
Choo JoanZhao Joseph JLau Mai ChanRaimondi AlessandraYim Willa Wen-YouRanganathan SruthiZhu KexinTan Crystal Tze YingChin Hui XianTeo Chong BoonFong Khi YungTay Ryan Yong KiatLee Jia-Ying JoeyLoo Lit-HsinManca PaoloMorano FedericaPrisciandaro MicheleRandon GiovanniDamonte CamillaMicarelli ElisaLeoni GuidoScarselli ElisaLonardi SaraCremolini ChiaraMarmorino FedericaLim Jeffrey Chun TattNeo Zhen WeiWee FeliciaChong Li YenJoseph Craig RyanBalachander AkhilaLim Diana GsHwang You YiRenia LaurentBiswas Subhra KumarTan DavidYeong Joe P SSundar RaghavPietrantonio Filippo - Gliomas are the most common type of primary brain tumors. Their management options and outcomes depend significantly on the underlying molecular-marker profile. Traditionally, molecular markers are determined through pathological testing on a tissue specimen acquired through biopsy. Several Magnetic Resonance Imaging (MRI) based Deep Learning (DL) methods offer a promising, non-invasive approach to predict these markers. However, they often require high-quality, well-annotated datasets. To support this need, we present a well-curated brain tumor dataset developed at The University of Texas Southwestern (UTSW) Medical Center. This dataset includes multi-contrast-MRI, demographics, molecular-markers, and multi-label tumor segmentations for 625 patients treated at UTSW between 2006 and 2023. Each patient record contains four MRI contrasts: pre-contrast-T1w, post-contrast-T1w, T2w, and T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR) images. The dataset also provides comprehensive genetic information, including IDH mutation-status, 1p19q co-deletion, MGMT promoter methylation, tumor-type, and tumor-grade. This dataset offers a valuable resource for exploring the relationship between MRI characteristics and tumor genetics. It also serves as a robust benchmark for developing and validating DL models for various downstream tasks. - Source: PubMed
Publication date: 2026/04/22
Reddy Divya DSaadat NiloufarHolcomb James MWagner Benjamin CTruong Nghi CBowerman JasonHatanpaa Kimmo JPatel Toral RPinho Marco CYu FangZhang KuanLodhi SadeemMadhuranthakam Ananth JBangalore Yogananda Chandan GaneshMaldjian Joseph A - DNA methylation is a key regulator of tissue-specific gene expression, cell differentiation, and development. In mammals, DNA methylation predominantly occurs as 5-methylcytosine (5mC) at CpG dinucleotides. DNA methylation is a dynamic and reversible process. Increasing evidence indicates that 5-hydroxymethylcytosine (5hmC), an oxidation product of 5mC, plays important roles in chromatin organization and gene regulation. Aberrant 5hmC levels have been associated with various neurological disorders and cancer types. Despite its biological relevance, accurate quantification of 5hmC at single-CpG resolution remains challenging due to its low abundance and methodological limitations of existing detection approaches. - Source: PubMed
Publication date: 2026/04/20
Pühringer KatharinaCzarda PhilippIluca SebastianFehringer BennoSherovski PeceOhindovschi AngelicaHainfellner AndreasReissig LukasWeninger Wolfgang JCichna-Markl Margit - Isocitrate dehydrogenase-wildtype glioblastoma (IDHwtGB) is the most common primary malignant brain tumor in adults, with a universally poor prognosis. For survival and growth under conditions of the tumor microenvironment, glioblastoma cells require antioxidant glutathione (GSH) and its metabolic precursor cystathionine (Cth) to maintain redox balance. We aimed to characterize GSH and Cth in vivo, in IDHwtGB patients, using edited MR spectroscopy (MRS). Our goal was to evaluate their tumor-molecular-status-dependent alterations and assess their potential as biomarkers for therapies targeting redox imbalance, following a reproducibility assessment of the measurement protocol in healthy subjects. - Source: PubMed
Publication date: 2026/04/18
Alcicek SeymaManzhurtsev AndreiThomas Dennis CDivé IrisWeber Katharina JPrinz VincentJussen DanielDeelchand Dinesh KOeltzschner GeorgRonellenfitsch Michael WSteinbach Joachim PHattingen ElkePilatus UlrichWenger Katharina J