ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 32 citations in OpenAlex.
- NAPRT Expression and Epigenetic Regulation in Pediatric Rhabdomyosarcoma as a Potential Biomarker for NAMPT Inhibition.Molecular cancer therapeutics · 2026Article
- HDAC8 inhibition targets STAT3-MYC axis and synergizes with Venetoclax in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Nicotinamide N-Methyl Transferase (NNMT) Sustains Innate Sensitivity to NAMPT Inhibition in YAP-dependent Stem-like/Mesenchymal Prostate Cancer.International journal of biological sciences · 2026Article
- Systematic Evaluation of GAPs and GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies.Cancer discovery · 2025Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- SIRT5 inhibition impairs mitochondrial metabolism and enhances venetoclax-induced elimination of acute myeloid leukemia cells.Leukemia · 2025Article
- NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk myeloid malignancies withBlood neoplasia · 2025Article
- Review
- The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.Cancers · 2025Review
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Crotonylation of MCM6 enhances chemotherapeutics sensitivity of breast cancer via inducing DNA replication stress.Cell proliferation · 2025Article
- Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- ZNF521 promotes acute myeloid leukemogenesis by suppressing the expression and acetylation of SMC3.Heliyon · 2024Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia.The EMBO journal · 2023Review
- Histone regulator KAT2A acts as a potential biomarker related to tumor microenvironment and prognosis of diffuse large B cell lymphoma.BMC cancer · 2023Article
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- The role of mammalian Sirtuin 6 in cardiovascular diseases and diabetes mellitus.Frontiers in physiology · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 2 institutions in 1 country.
Funding
Abstract
purposeNicotinamide phosphoribosyltransferase (NAMPT) inhibitors (NAMPTi) are currently in development, but may be limited as single-agent therapy due to compound-specific toxicity and cancer metabolic plasticity allowing resistance development. To potentially lower the doses of NAMPTis required for therapeutic benefit against acute myeloid leukemia (AML), we performed a genome-wide CRISPRi screen to identify rational disease-specific partners for a novel NAMPTi, KPT-9274. EXPERIMENTAL
designCell lines and primary cells were analyzed for cell viability, self-renewal, and responses at RNA and protein levels with loss-of-function approaches and pharmacologic treatments.
resultsWe identified two histone deacetylases (HDAC),
conclusionsOur findings provide evidence that HDAC8 inhibition- or shSIRT6-induced DNA repair deficiencies are potently synergistic with NAMPT targeting, with minimal toxicity toward normal cells, providing a rationale for a novel-novel combination-based treatment for AML.
Indexed as
Identifiers
What OpenQuestion holds
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.