ArticleOncotarget2015
The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- The Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL.Cells · 2025Article
- Dichloroacetate enhances Chemo-sensitivity in wild-type P53 breast cancer cells by modulating ABCG2 and NKG2DL.Scientific reports · 2025Article
- Targeting mitochondrial bioenergetics by combination treatment with imatinib and dichloroacetate in human erythroleukemic K‑562 and colorectal HCT‑116 cancer cells.International journal of oncology · 2024Article
- DR5 Up-Regulation Induced by Dichloroacetate Sensitizes Tumor Cells to Lipid Nanoparticles Decorated with TRAIL.Journal of clinical medicine · 2023Article
- FBP1-Altered Carbohydrate Metabolism Reduces Leukemic Viability through Activating P53 and Modulating the Mitochondrial Quality Control System In Vitro.International journal of molecular sciences · 2022Article
- Article
- The metabolism of cells regulates their sensitivity to NK cells depending on p53 status.Scientific reports · 2022Article
- Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1).Scientific reports · 2022Article
- Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesotheliomaFrontiers in pharmacology · 2022Article
- From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy.International journal of molecular sciences · 2021Review
- Article
- Article
- Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies.Blood advances · 2020Article
- Mutations in theCancers · 2019Article
- Metabolic stress controls mutant p53 R248Q stability in acute myeloid leukemia cells.Scientific reports · 2019Article
- Dichloroacetate Ameliorates Cardiac Dysfunction Caused by Ischemic Insults Through AMPK Signal Pathway-Not Only Shifts Metabolism.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Mitochondrial Complex I activity signals antioxidant response through ERK5.Scientific reports · 2018Article
- Changes in metabolism affect expression of ABC transporters through ERK5 and depending on p53 status.Oncotarget · 2018Article
- Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors.Theranostics · 2018Article
- The PDK1 Inhibitor Dichloroacetate Controls Cholesterol Homeostasis Through the ERK5/MEF2 Pathway.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Manipulation of metabolic pathways in hematological cancers has therapeutic potential. Here, we determined the molecular mechanism of action of the metabolic modulator dichloroacetate (DCA) in leukemic cells. We found that DCA induces the AMP-activated protein kinase (AMPK)/p53 pathway with increased efficacy in tumors expressing wild type (wt p53). Clinically relevant, low concentrations of doxorubicin synergize in vitro and in vivo with DCA to further enhance p53 activation and to block tumor progression. Leukemia cell lines and primary leukemic cells containing mutant p53 are resistant to the above-described combination approach. However, DCA synergized with the Hsp90 inhibitor 17-AAG to specifically eliminate these cells. Our studies strongly indicate that depending on the p53 status, different combination therapies would provide better treatment with decreased side effects in hematological cancers.
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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.