Copper Chelation
Copper is a trace element tightly regulated within our bodies. One of copper’s functions is to promote angiogenesis (formation of new blood vessels), meaning it can also promote malignant angiogenesis, enabling tumor growth, invasion and metastasis.
Also known by these names
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Key Points
- Copper promotes angiogenesis (formation of new blood vessels in our bodies.
- Researchers are finding that copper chelation promotes tumor dormancy and helps prevent relapse, especially among women with triple-negative breast cancer.
- Chelating drugs require a prescription and carry a risk of side effects.
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Treating the Cancer
Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action
Over the years, researchers have studied how and whether removing copper from the body through a process called “chelation” affects tumor angiogenesis. Using the copper-chelating drug tetrathiomolybdate (TM) in both laboratory studies and in people with advanced cancer, researchers are finding that copper chelation promotes tumor dormancy and helps prevent relapse, especially among women with triple-negative breast cancer (TNBC).
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Some integrative oncology care physicians, such as Brian Bouch, MD, have used copper chelation in their practices and have noted good if not remarkable results in some of their patients. Some of these physicians also have their patients follow a low-copper diet.
Clinical Evidence
Breast Cancer
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- Copper chelation with tetrathiomolybdate (TM) promotes tumor dormancy and helps prevent relapse, especially among women with triple-negative breast cancer.
- Studies using TM in breast cancer at high risk of recurrence, researchers concluded that copper depletion seems to create an inhospitable environment for tumor progression and promote progression-free survival, especially in triple-negative disease, with low toxicity.
- Copper chelation with TM improved event-free survival and progression-free survival and decreased cancer biomarkers
Colorectal Cancer
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TM was studied in combination with irinotecan, 5-fluorouracil, and leucovorin (IFL) in patients with metastatic colorectal cancer. The overall response rate) was 25 percent, and the median time to progressionwas 5.6 months.
Kidney Cancer
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- in a phase 2 trial in patients with advanced kidney cancer using TM for copper chelation, TM was well tolerated and consistently depleted copper. Clinical activity was limited to stable disease for a median of 34.5 weeks.
Prostate Cancer
- Slower PSA progression was seen in a small clinical trial of TM, but with uncertain clinical significance.
- Copper depletion with TM did not delay disease progression in a small clinical trial of patients with asymptomatic metastatic hormone-refractory prostate cancer.
Unspecified Metastatic Cancer
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- TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.”
Lab and Animal Evidence
Both the serum and tumor copper levels are elevated in a variety of malignancies, including both solid tumor and blood cancer. Elevated copper levels have been shown to be directly correlated to cancer progression.
Anticancer effects were seen in prostate cancer cells from pyrrolidine dithiocarbamate (PDTC) but not TM.
Cautions
Chelating drugs require a prescription, carry a risk of side effects and should be taken only as directed by a qualified healthcare professional who will monitor their use.
Chelation with TM may promote breast cancer stem cells, potentially leading to recurrence.
Integrative Programs, Protocols and Medical Systems
- Programs and protocols
- Block program: off-label use for cancer to inhibit angiogenesis
- McKee guidelines on copper chelation.
- McKinney protocols
- Goodman VL, Brewer GJ, Merajver SD. Copper deficiency as an anti-cancer strategy. Endocrine-related Cancer. 2004 (11). 255-26004 Jun;11(2):255-63.3; Jain S, Cohen J et al. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. Annals of Oncology. 2013 Jul;24(6):1491–1498.
- Food for Breast Cancer: Food and Other Sources of Copper Exposure. July 2015. Viewed September 28, 2018.
- Goodman VL Brewer GJ, Merajver SD. Copper deficiency as an anti-cancer strategy. Endocrine-related Cancer. 2004 Jun;11(2):255-63; Jain S, Cohen J et al. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. Annals of Oncology. 2013 Jul;24(6):1491–1498.
- Nackos E, Kornhauser N et al. Altering the tumor microenvironment: a phase II study of copper depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence. Journal of Clinical Oncology, ASCO Annual Meeting Abstract 11008, June 2015; Chan N, Willis A et al. Influencing the tumor microenvironment: a phase ii study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases. Clinical Cancer Research. 2017 Feb 1;23(3):666-676.
- Chan N, Willis A et al. Influencing the tumor microenvironment: a phase II study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases. Clinical Cancer Research. 2017 Feb 1;23(3):666-676.
- Gartner EM, Griffith KA et al. A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer. Invest New Drugs. 2009 Apr;27(2):159-65.
- Bruce G. Redman, Peg Esper, Quintin Pan, Rodney L. Dunn, Hero K. Hussain, Thomas Chenevert, George J. Brewer and Sofia D. Merajver. Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer. Clinical Cancer Research. May 1 2003 9 (5) 1666-1672.
- Lin J, Zahurak M et al. A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-naïve prostate cancer. Urologic Oncology. 2013 Jul;31(5):581-8.
- Henry NL, Dunn R et al. Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone-refractory prostate cancer. Oncology. 2006;71(3-4):168-75.
- Brewer, GJ, et al. Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: phase I study. Clinical Cancer Research. January 1 2000 6 (1) 1-10.
- Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treatment Reviews. 2009 Feb;35(1):32-46.
- Chen D, Peng F et al. Inhibition of prostate cancer cellular proteasome activity by a pyrrolidine dithiocarbamate-copper complex is associated with suppression of proliferation and induction of apoptosis. Frontiers in Bioscience. 2005 Sep 1;10:2932-9.
- Lu H, Samanta D et al. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proceedings of the National Academy of Sciences USA. 2015 Aug 18;112(33):E4600-9.
- McKinney N. Naturopathic Oncology, 3rd Edition. Victoria, BC, Canada: Liaison Press. 2016. p. 316.
- Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009.
- McKee D. The Role of Copper in the Angiogenesis Process and Chelating Copper as a Nutritional Anti-angiogenic Strategy + Other Available Anti-angiogenic Agents Useful in the Control of Cancer. Used with permission of the author.
- McKinney N. Naturopathic Oncology, 3rd Edition. Victoria, BC, Canada: Liaison Press. 2016.
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