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| http://dx.doi.org/10.18632/oncotarget.5860 | DOI Listing |
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DOT1L mediates stem cell maintenance and represents a therapeutic vulnerability in cancer.
Cancer Res
December 2024
Georgetown University, Washington, DC, United States.
Tumor-initiating cancer stem cells (CSC) pose a challenge in human malignancies since they are largely treatment resistant and can seed local recurrence and metastasis. Epigenetic mechanisms governing cell fate decisions in embryonic and adult stem cells are deregulated in CSCs. This review focuses on the methyltransferase DOT1L, which methylates H3K79 and is a key epigenetic regulator governing embryonic organogenesis and adult tissue stem cell maintenance.
View Article and Find Full Text PDFAntitumor activity of selenopsammaplin A analog (SPA-10091-HCl) via histone methyltransferase DOT1L degradation and apoptosis induction in castration-resistant prostate cancer cells.
Eur J Pharm Sci
February 2025
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
Castrate-resistant prostate cancer (CRPC) is one of the most difficult cancers in men and is characterized by a poor prognosis and a high risk of metastasis. The overexpression of the disruptor of telomeric silencing 1-like (DOT1L), which is a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), has been related to poor outcomes in patients with CRPC. Therefore, targeting DOT1L is considered a potential therapeutic approach to overcome the significant medical challenges of CRPC.
View Article and Find Full Text PDFSynergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor.
Cancers (Basel)
November 2024
Cancer Section, Development Biology and Cancer Programme, UCL GOS Institute of Child Health, London WC1N 1EH, UK.
KMT2A-rearranged leukemias are a highly aggressive subset of acute leukemia, characterized by poor prognosis and frequent relapses despite intensive treatment. Menin inhibitors, which target the critical KMT2A-menin interaction driving leukemogenesis, have shown promise in early clinical trials. However, resistance to these inhibitors, often driven by menin mutations or alternative oncogenic pathways, remains a significant challenge.
View Article and Find Full Text PDFSomatic mutational landscape reveals mutational signatures and significantly mutated genes of cancer immunotherapeutic outcome and sex disparities.
Front Immunol
November 2024
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.
Background: Currently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators.
View Article and Find Full Text PDFSystematic identification of therapeutic targets for coronary artery calcification: an integrated transcriptomic and proteomic Mendelian randomization.
Front Cardiovasc Med
October 2024
Department of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Article Synopsis
- Coronary artery calcification (CAC) increases the risk of heart-related issues, yet no drugs have been found effective for its treatment; this study aims to discover potential therapeutic targets using Mendelian randomization.
- By analyzing genetic data from over 26,000 individuals, 671 genes were linked to CAC risk through transcriptomic analysis, while 15 proteins were identified in proteomic analysis; 23 potential drug targets for CAC were discovered.
- Key candidates for further investigation include ULK3, DOT1L, and AMH as they showed promise for drug repurposing to treat CAC.
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