Literature DB >> 23263938

Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP.

Stephen B Strum1, Orn Adalsteinsson, Richard R Black, Dmitri Segal, Nancy L Peress, James Waldenfels.   

Abstract

The uptake of fluorodeoxyglucose Positron Emission Tomography in the tumors of various cancer types demonstrates the key role of glucose in the proliferation of cancer. Dichloroacetate is a 2-carbon molecule having crucial biologic activity in altering the metabolic breakdown of glucose to lactic acid. Human cell line studies show that dichloroacetate switches alter the metabolomics of the cancer cell from one of glycolysis to oxidative phosphorylation, and in doing so restore mitochondrial functions that trigger apoptosis of the cancer cell. Reports of dichloroacetate in human subjects are rare. The authors contacted individuals from Internet forums who had reported outstanding anti-cancer responses to self-medication with dichloroacetate. With informed consent, complete medical records were requested to document response to dichloroacetate, emphasizing the context of monotherapy with dichloroacetate. Of ten patients agreeing to such an evaluation, only one met the criteria of having comprehensive clinic records as well as pathology, imaging and laboratory reports, along with single agent therapy with dichloroacetate. That individual is the focus of this report. In this case report of a man with documented relapse after state-of-the-art chemotherapy for non-Hodgkin's lymphoma, a significant response to dichloroacetate is documented with a complete remission, which remains ongoing after 4 years. Dichloroacetate appears to be a novel therapy warranting further investigation in the treatment of cancer.

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Year:  2012        PMID: 23263938     DOI: 10.1007/s10863-012-9496-2

Source DB:  PubMed          Journal:  J Bioenerg Biomembr        ISSN: 0145-479X            Impact factor:   2.945


  33 in total

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Journal:  Science       Date:  1956-08-10       Impact factor: 47.728

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Journal:  Science       Date:  1956-02-24       Impact factor: 47.728

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Journal:  Cancer Cell       Date:  2007-01       Impact factor: 31.743

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Journal:  J Inherit Metab Dis       Date:  1986       Impact factor: 4.982

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Journal:  Arch Dis Child       Date:  1997-12       Impact factor: 3.791

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Journal:  J Biol Chem       Date:  1981-08-25       Impact factor: 5.157

8.  The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models.

Authors:  Robert A Gatenby; Edward T Gawlinski
Journal:  Cancer Res       Date:  2003-07-15       Impact factor: 12.701

9.  Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation.

Authors:  Wengang Cao; Saif Yacoub; Kathleen T Shiverick; Kazunori Namiki; Yoshihisa Sakai; Stacy Porvasnik; Cydney Urbanek; Charles J Rosser
Journal:  Prostate       Date:  2008-08-01       Impact factor: 4.104

Review 10.  Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.

Authors:  E D Michelakis; L Webster; J R Mackey
Journal:  Br J Cancer       Date:  2008-09-02       Impact factor: 7.640

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  21 in total

Review 1.  Pyruvate and Metabolic Flexibility: Illuminating a Path Toward Selective Cancer Therapies.

Authors:  Kristofor A Olson; John C Schell; Jared Rutter
Journal:  Trends Biochem Sci       Date:  2016-02-10       Impact factor: 13.807

Review 2.  Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.

Authors:  Margaret O James; Stephan C Jahn; Guo Zhong; Marci G Smeltz; Zhiwei Hu; Peter W Stacpoole
Journal:  Pharmacol Ther       Date:  2016-10-19       Impact factor: 12.310

Review 3.  Metabolic targets for cancer therapy.

Authors:  Lorenzo Galluzzi; Oliver Kepp; Matthew G Vander Heiden; Guido Kroemer
Journal:  Nat Rev Drug Discov       Date:  2013-10-11       Impact factor: 84.694

Review 4.  The Warburg effect: evolving interpretations of an established concept.

Authors:  Xiaozhuo Chen; Yanrong Qian; Shiyong Wu
Journal:  Free Radic Biol Med       Date:  2014-09-30       Impact factor: 7.376

5.  Rational combination with PDK1 inhibition overcomes cetuximab resistance in head and neck squamous cell carcinoma.

Authors:  Haiquan Lu; Yang Lu; Yangyiran Xie; Songbo Qiu; Xinqun Li; Zhen Fan
Journal:  JCI Insight       Date:  2019-10-03

6.  Perturbation of cellular oxidative state induced by dichloroacetate and arsenic trioxide for treatment of acute myeloid leukemia.

Authors:  Ashkan Emadi; Mariola Sadowska; Brandon Carter-Cooper; Vishal Bhatnagar; Isabella van der Merwe; Mark J Levis; Edward A Sausville; Rena G Lapidus
Journal:  Leuk Res       Date:  2015-04-30       Impact factor: 3.156

Review 7.  Restoration of mitochondria function as a target for cancer therapy.

Authors:  Tariq A Bhat; Sandeep Kumar; Ajay K Chaudhary; Neelu Yadav; Dhyan Chandra
Journal:  Drug Discov Today       Date:  2015-03-09       Impact factor: 7.851

8.  ASCT2 (SLC1A5) is an EGFR-associated protein that can be co-targeted by cetuximab to sensitize cancer cells to ROS-induced apoptosis.

Authors:  Haiquan Lu; Xinqun Li; Yang Lu; Songbo Qiu; Zhen Fan
Journal:  Cancer Lett       Date:  2016-07-19       Impact factor: 8.679

Review 9.  Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication.

Authors:  Minjong Lee; Jung-Hwan Yoon
Journal:  World J Biol Chem       Date:  2015-08-26

10.  A phase I study of the first-in-class antimitochondrial metabolism agent, CPI-613, in patients with advanced hematologic malignancies.

Authors:  Timothy S Pardee; King Lee; John Luddy; Claudia Maturo; Robert Rodriguez; Scott Isom; Lance D Miller; Kristin M Stadelman; Denise Levitan; David Hurd; Leslie R Ellis; Robin Harrelson; Megan Manuel; Sarah Dralle; Susan Lyerly; Bayard L Powell
Journal:  Clin Cancer Res       Date:  2014-08-27       Impact factor: 12.531

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