Journal article
Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks
Journal of experimental & clinical cancer research, v 43(1), 12
05 Jan 2024
PMID: 38183103
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Targeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 (EZH2), and lysine-specific demethylase 1 (LSD1), and various signaling pathways essential for cancer cell growth and progression. These specific epigenetic regulators were chosen for review due to their targetability via pharmacological intervention and clinical relevance. Several studies have demonstrated improved efficacy from the dual inhibition of the epigenetic regulators and signaling kinases. Overall, the interactions between epigenetic regulators and kinase signaling pathways are likely influenced by several factors, including individual glioma subtypes, preexisting mutations, and overlapping/interdependent functions of the chromatin regulators. The insights gained by understanding how the genome and epigenome cooperate in high-grade gliomas will guide the design of future therapeutic strategies that utilize dual inhibition with improved efficacy and overall survival.
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Details
- Title
- Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks
- Creators
- Lea M Stitzlein - The University of Texas MD Anderson Cancer CenterJack T Adams - The University of Texas MD Anderson Cancer CenterErin N Stitzlein - Drexel UniversityRichard W Dudley - University of FindlayJoya Chandra (Corresponding Author) - The University of Texas MD Anderson Cancer Center
- Publication Details
- Journal of experimental & clinical cancer research, v 43(1), 12
- Publisher
- Springer Nature
- Grant note
- P50 CA127001 / NCI NIH HHS TL1 TR003169 / NIH HHS P50 CA127001 / NIH HHS TL1 TR003169 / NCATS NIH HHS R61/R33NS111058 / NIH HHS R21 NS093387 / NIH HHS R33 NS111058 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Obstetrics and Gynecology
- Web of Science ID
- WOS:001137105300001
- Scopus ID
- 2-s2.0-85181455651
- Other Identifier
- 991022202490004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology