ArticlePloS one2012
Cross-species functional genomic analysis identifies resistance genes of the histone deacetylase inhibitor valproic acid.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- The anticonvulsant and mood-stabilizing drug valproic acid attractsbioRxiv : the preprint server for biology · 2025Article
- Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression.International journal of molecular sciences · 2023Article
- Parental energy-sensing pathways control intergenerational offspring sex determination in the nematode Auanema freiburgensis.BMC biology · 2021Article
- Therapeutic Use of Valproic Acid and All-Trans Retinoic Acid in Acute Myeloid Leukemia-Literature Review and Discussion of Possible Use in Relapse after Allogeneic Stem Cell Transplantation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
- Article
- Modulation of phospho-proteins by interferon-alpha and valproic acid in acute myeloid leukemia.Journal of cancer research and clinical oncology · 2019Article
- Found in Translation: The Utility ofBrain sciences · 2019Review
- Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia.Oncotarget · 2016Article
- HSP90AB1: Helping the good and the bad.Gene · 2016Review
- Cells adapt to the epigenomic disruption caused by histone deacetylase inhibitors through a coordinated, chromatin-mediated transcriptional response.Epigenetics & chromatin · 2015Article
- Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy.Leukemia · 2015Review
- Biomarkers of treatment toxicity in combined-modality cancer therapies with radiation and systemic drugs: study design, multiplex methods, molecular networks.International journal of molecular sciences · 2014Review
- Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders.Molecular neurobiology · 2013Review
- Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents.Clinical epigenetics · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of successful epigenetic reprogramming in cancer are not well characterized as they involve coordinated removal of repressive marks and deposition of activating marks by a large number of histone and DNA modification enzymes. Here, we have used a cross-species functional genomic approach to identify conserved genetic interactions to improve therapeutic effect of the histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in more than 20% of patients with advanced acute myeloid leukemia (AML). Using a bidirectional synthetic lethality screen revealing genes that increased or decreased VPA sensitivity in C. elegans, we identified novel conserved sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which demonstrates a functional relationship between protein acetylation and lysine-specific methylation. The synthetic lethal screen identified resistance programs that compensated for the HDACi-induced global hyper-acetylation, and confirmed MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs represent promising novel targets for refinement of combinatorial epigenetic anti-cancer therapy.
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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.