ArticleCancers2020
Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.BMC cancer · 2024Article
- Integrative analysis and risk model construction for super‑enhancer‑related immune genes in clear cell renal cell carcinoma.Oncology letters · 2024Article
- Curcumin inhibits the proliferation and migration of osteosarcoma by regulating the expression of superZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Article
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance.Cell death & disease · 2023Article
- Review
- Superenhancers as master gene regulators and novel therapeutic targets in brain tumors.Experimental & molecular medicine · 2023Review
- Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics.Cell death and differentiation · 2022Article
- Mcl-1 levels critically impact the sensitivities of human colorectal cancer cells to APG-1252-M1, a novel Bcl-2/Bcl-XNeoplasia (New York, N.Y.) · 2022Article
- Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation.Cell death & disease · 2021Article
- Critical View of Novel Treatment Strategies for Glioblastoma: Failure and Success of Resistance Mechanisms by Glioblastoma Cells.Frontiers in cell and developmental biology · 2021Review
- Neferine induces p38 MAPK/JNK1/2 activation to modulate melanoma proliferation, apoptosis, and oxidative stress.Annals of translational medicine · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM. We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction with features of apoptosis, including disruption of mitochondrial membrane potential followed by activation of caspases. Mechanistically, THZ1 elicited a profound disruption of the Mcl-1 enhancer region, leading to a sustained suppression of Mcl-1 transcript and protein levels, respectively. Mechanism experiments suggest involvement of Mcl-1 in the cell death elicited by the combination treatment. Finally, the combination treatment of ABT263 and THZ1 resulted in enhanced growth reduction of tumors without induction of detectable toxicity in two patient-derived xenograft models of GBM in vivo. Taken together, these findings suggest that combined epigenetic targeting of Mcl-1 along with Bcl-2/Bcl-xL is potentially therapeutically feasible.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.