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 BCCT advisor Brian Bouch, MD, have used copper chelation in their practices and have noted good or even 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
See Breast Cancer.
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.
See Colorectal Cancer.
Esophageal cancer
- No association between decreased level of ceruloplasmin with recurrence-free survival or overall survival in patients with resectable, locally advanced esophageal cancer
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.
See Kidney Cancer.
Prostate Cancer
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- 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.
See 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
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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.
Access
TM must be compounded by a trained compounding pharmacist based on your doctor's prescription. In compounding, "ingredients are mixed together in the exact strength and dosage form required by the patient." TM has a short shelf life, so it is provided in one- to two-month supplies. The first month of treatment requires higher doses and the cost is about $275. After that, monthly maintenance supply costs about $200 to $235. At the time of this writing, TM is not covered by insurance. Ceruloplasmin testing is necessary while you are on TM, and testing may not be covered by insurance plans.
Pharmacy Solutions in Michigan is a compounding pharmacy that compounds TM. Their contact number is 877-797-6567.
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
- Bastyr University Integrative Oncology Research Center protocol for stage IV breast cancer
- Block program: off-label use for cancer to inhibit angiogenesis
- McKee guidelines on copper chelation.
- McKinney protocols
Naturopathic oncologist and BCCT advisor Jen Green, ND, FABNO, and BCCT senior researcher Laura Pole, RN, MSN, OCNS, July 15, 2019: Zinc and copper are inversely related: as zinc levels increase, copper levels decrease. A higher copper-to-zinc ratio is associated with an increased risk of some cancers, likely because copper levels increase with angiogenesis. The situation is often exacerbated by zinc depletion from chemotherapy, malabsorption, head radiation or chronic diarrhea (all common in cancer patients). Zinc is important for white blood cell function, so I (Dr. Green) am a fan of zinc supplementation.
High doses of zinc can lower copper levels, and it is used in lowering copper levels in Wilson's disease. To our knowledge it has not been used alone in clinical trials to reduce copper levels in people with cancer. I (Dr. Green) have tried high-dose zinc with molybdenum to lower copper levels in my patients, and that strategy is able to get ceruloplasmin to the low end of the normal range. However, to actually get ceruloplasmin into the 8 to 17 mg/dL range (below normal range) that was used in the Cornell study in triple negative breast cancer survivors, one has to use TM. Thankfully, TM is still currently available from one pharmacy in the US.
Written by Laura Pole, RN, MSN, OCNS, and reviewed by Nancy Hepp, MS; most recent update on July 15, 2019.
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- PCCA. What is Compounding? Viewed June 7, 2019.
- 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.
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- 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.
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