The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors
Open accessAbstract
Background Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. Design We conducted an open-label study of oral DCA in 15 adults with recurrent WHO grade III - IV gliomas or metastases from a primary cancer outside the central nervous system. The primary objective was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment, defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable to DCA, based on the National Cancer Institute's Common Toxicity Criteria for Adverse Events, version 4.0. Secondary objectives involved safety, tolerability and hypothesis-generating data on disease status. Dosing was based on haplotype variation in glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. Results Eight patients completed at least 1 four week cycle. During this time, no dose-limiting toxicities occurred. No patient withdrew because of lack of tolerance to DCA, although 2 subjects experienced grade 0-1 distal parasthesias that led to elective withdrawal and/or dose-adjustment. All subjects completing at least 1 four week cycle remained clinically stable during this time and remained on DCA for an average of 75.5 days (range 26-312). Conclusions Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases. The importance of genetic-based dosing is confirmed and should be incorporated into future trials of chronic DCA administration.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“This knowledge has led to the testing of drugs that inhibit glycolysis such as dichloroacetic acid (DCA), which inhibits PDK activity (Dunbar et al., 2014).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Dunbar et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,686
A New Statistical Method for Haplotype Reconstruction from Population Data
Stephens, M., Smith, N. J. C., & Donnelly, P. (2001) · The American Journal of Human Genetics · doi:10.1086/319501 · Cited by 7,512
Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., DeGroot, J. F., Wick, W., Gilbert, M. R., Lassman, A. B., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.3541 · Cited by 3,890
The clinical evaluation of chemotherapeutic agents in cancer
Karnofsky, D. A. (1949) · Medical Entomology and Zoology · Cited by 2,933
Response criteria for phase II studies of supratentorial malignant glioma.
Macdonald, D. R., Cascino, T. L., Schold, S. C., & Cairncross, J. G. (1990) · Journal of Clinical Oncology · doi:10.1200/jco.1990.8.7.1277 · Cited by 2,409
Bonnet, S., Archer, S. L., Allalunis‐Turner, J., Haromy, A., Beaulieu, C., Thompson, R. B., Lee, C. T., Lopaschuk, G. D., Puttagunta, L., Bonnet, S. B., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.10.020 · Cited by 1,552
Yung, W. K. A., Albright, R. E., Olson, J., Fredericks, R., Fink, K., Prados, M. D., Brada, M., Spence, A., Hohl, R. J., Shapiro, W., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1316 · Cited by 929 · cited 1×
“Recurrent malignant brain tumors (RMBTs), whether from primary malignant gliomas, or from metastasis to the central nervous system (CNS), have a poor prognosis [1, 2].”
Metabolic Modulation of Glioblastoma with Dichloroacetate
Michelakis, E. D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E. B., Maguire, C., Gammer, T.-L., Mackey, J. R., Fulton, D. S., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000677 · Cited by 744
Research works printed but not linked: 1
- Mitchell G, Lambert M, Tanguay R. Hypertyrosinemia (1995) In Schriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, Inc., Health Professions Division, New York, pp. 1077–106
Cited by
Sorted by citations
Items 201–242 of 242
Dichloroacetate- Phase 1 Trial in Adults with Malignant Brain Tumors
Lorenzo, R. J., & Jahn, S. C. (2015) · Postdoc Journal · doi:10.14304/surya.jpr.v3n2.5 · Cited by 1
Chu, Q. S.-C., Sangha, R. S., Spratlin, J. L., Vos, L. J., Mackey, J. R., McEwan, A. J. B., Venner, P. M., & Michelakis, E. D. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu331.38 · Cited by 1
Pharmacological interventions part IV: Metabolic modifiers
Koltai, T., Reshkin, S. J., & Harguindey, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819059-3.00016-2 · Cited by 1
Wu, X. (2016) · IUScholarWorks (Indiana University) · doi:10.7912/c2s89r · Cited by 1
Therapeutic Modulation of Cancer Metabolism with Dichloroacetate and Metformin
Ward, N. P. (2017) · Digital Commons - University of South Florida (University of South Florida) · Cited by 1
Powell, S. F., Mazurczak, M. A., Dib, E. G., Bleeker, J. S., Geeraerts, L., Tinguely, M., Lohr, M. M., McGraw, S. C., Jensen, A. W., Ellison, C. A., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-1132811/v1 · Cited by 1
Parczyk, J., Ruhnau, J., Pelz, C., Schilling, M., Wu, H., Piaskowski, N. N., Eickholt, B. J., Kühn, H., Danker, K., & Klein, A. (2020) · Research Square · doi:10.21203/rs.3.rs-88933/v1 · Cited by 1
Mitochondria : a target for anticancer therapy
Kruspig, B. (2014) · Figshare
Barkovskaya, A. (2015) · NORA - Norwegian Open Research Archives
Resistance of Glioblastomas to Radiation Therapy
Shen, H. M., & Hau, E. K. C. (2016) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-46505-0_3
Targeting Antioxidant Systems to Treat Pancreatic Cancer
Fazzari, F. G. T. (2018) · TSpace (University of Toronto)
Dichloressigsäure und ihre Salze [MAK Value Documentation in German language, 2019]
Hartwig, A., & MAK Commission (2019) · The MAK-Collection for Occupational Health and Safety · doi:10.1002/3527600418.mb7943verd0067
The time has come to pull renal cancer’s sweet tooth
Kinnaird, A. S., & Michelakis, E. D. (2019) · Translational Cancer Research · doi:10.21037/tcr.2018.12.31
Metal complexes as chemotherapeutic agents
Deo, K. M., & Aldrich-Wright, J. R. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823144-9.00050-9
Exploring glycolytic adaptations in cancer cells
Matos, B., Howl, J., Jerónimo, C., & Fardilha, M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91704-9.00014-8
Parczyk, J., Ruhnau, J., Pelz, C., Schilling, M., Wu, H., Piaskowski, N. N., Eickholt, B. J., Kühn, H., Danker, K., & Klein, A. (2021) · Figshare · doi:10.6084/m9.figshare.14524716
Does modifying energy metabolism alter cellular signaling and proliferation in KRAS mutant NSCLCs?
Köker, Ş. C., & Doğan, İ. (2025) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2025-0030
Amato, L., Rosa, C. D., Omodei, D., Tufano, C. C., Buono, R., Tuccillo, C., Roviello, G. N., Spinelli, M., Fontanarosa, C., Papaccio, F., et al. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.168014
Zheng, R., Tan, J., Cao, X., Wang, S., Dai, Q., Zhang, C., Wang, F., Yi, J., Song, L., & Dai, A. (2025) · Journal of Molecular Medicine · doi:10.1007/s00109-025-02589-y
Wang, T., Chen, S., & Hong, Z. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.09.058 · Cited by 1
Parczyk, J., Ruhnau, J., Pelz, C., Schilling, M., Wu, H., Piaskowski, N. N., Eickholt, B. J., Kühn, H., Danker, K., & Klein, A. (2021) · Figshare · doi:10.6084/m9.figshare.14524719
Martell, E., Kuzmychova, H., Senthil, H., Kaul, E., Chokshi, C., Venugopal, C., Anderson, C. M., Singh, S. K., & Sharif, T. (2024) · Figshare · doi:10.6084/m9.figshare.26602936
Mitochondria and resistance to targeted therapies
Porel, P., Kaur, M., Shah, S. S., & Aran, K. R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40535-8.00013-2
Study of tumor cell metabolism and its relationship with NK cell-mediated immunotherapy
Krzywińska, E. (2014) · theses.fr (ABES) · doi:10.70675/55685772z0acez4c8bzaf02z3edd2b0ef19f
Grentzmann, A., & Ketelhuth, D. F. J. (2026) · Cardiovascular Research · doi:10.1093/cvr/cvag088
Андреевна, Ш. А., Филимонова, М. В., Васильевна, С. О., Filatova, D. I., Александровна, П. Е., Kosachenko, A. O., Анатольевич, Н. К., Gorbachev, A. Y., Изместьева, О. С., Александрович, Р. В., et al. (2026) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2026-14-2-189-200
Mitochondrial targeting in cancer therapeutics
Patel, D., Kholiya, P. K., Patel, G., Patel, V., Patel, H., & Patel, J. K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-43870-7.00010-2
Iova, O.-M., Marin, G.-E., Răzniceanu, V., Mocrei-Rebrean, Ș.-M., Pintilie, S. R., Netea-Maier, R. T., & Berindan‐Neagoe, I. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125472
Patel, M. S., & Rideout, T. C. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1861016
Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring
Mendes, C. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-12166-0_2
Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance
Tan, Z., Wen, L., Guan, H., Bao, N., Wu, Z., Ji, X., & Lin, L. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1883537
Cho, M., & Song, M. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01798-w
Liu, G., Li, P., Li, Z., Li, J., Zhang, C., Wang, Y., Kang, W., & Ye, X. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70772 · Cited by 1
Fatty Acid Metabolism Rewires Glioblastoma Progression and Treg-Mediated Immune Resistance
Chowdhury, N. I., Ewida, H. A., Ahmed, M. S., & Villalba, H. (2026) · Cancers · doi:10.3390/cancers18162573
Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability
Sainero‐Alcolado, L., Lama, D., Alzrigat, M., & Arsenian‐Henriksson, M. (2026) · BioDrugs · doi:10.1007/s40259-026-00798-6
Redox Regulation in Glioblastoma: Mechanisms, Biomarkers, and Therapeutic Implications
Lamrabet, S., Houssaini, A. S., Bennis, S., & Hassani, R. A. E. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177940
Zhang, C., Wang, Y., Sun, Z., Wang, C., Hou, S., & Lin, N. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105586
Xiong, J., Mou, G., 泽塔多吉, Li, X., & Zhao, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1959235
Miao, Z., Hu, M., Li, K., Liu, J., Lin, W., Xiong, W., Zhang, H., & Zhang, Y. (2026) · Cancer Bioscience · doi:10.1016/j.cbs.2026.100011
Metadata
- Authors
- Dunbar, E. M., Coats, B. S., Shroads, A. L., Langaee, T., Lew, A., Forder, J. R., Shuster, J. J., Wagner, D. A., & Stacpoole, P. W.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Metabolic Solutions (US)
- Corresponding author
- Stacpoole, P. W.
- Venue
- Investigational New Drugs
- Published
- 2013-12-03
- Volume
- 32
- Issue
- 3
- Pages
- 452-464
- ISSN
- 0167-6997 (ISSN-L)
- 1573-0646
- PMC
- PMC4455946
- OpenAlex
- W2017529554
- Cited by
- 241
- References
- 50
- Citations by year
- 2026: 30 · 2025: 18 · 2024: 17 · 2023: 15 · 2022: 16 · 2021: 18 · 2020: 18 · 2019: 29 · 2018: 20 · 2017: 17 · 2016: 15 · 2015: 19 · 2014: 9
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Investigational New Drugs (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000064)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Keywords
- dichloroacetate, glioma, brain metastases, dose-limiting toxicity, drug safety and tolerability, mitochondrial oxidative metabolism
- MeSH terms
- Acetone, Adult, Aged, Alanine Transaminase, Antineoplastic Agents, Aspartate Aminotransferases, Brain Neoplasms, Breath Tests, Dichloroacetic Acid, Female, Glutathione Transferase, Haplotypes, Humans, Male, Maleates, Middle Aged, Pyruvic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
