Copper Chelation
Authors
 Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher
Read more Ms. Pole is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation and education services for more than 30 years. View profile.
 Nancy Hepp, MS, BCCT Project Manager
Read more Ms. Hepp is a science researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. View profile. Last updated November 23, 2020.
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Also known by these names
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Key Points
- Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
- 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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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.
Excess copper is a potent oxidant, causing the generation of harmful reactive oxygen species (ROS) in cells, a known driver of cancer development and growth. Serum copper levels have been found to be significantly increased in stomach, large intestine and lung solid neoplasias. Copper levels further increase with disease progression and decline with remission.
Over the years, researchers have studied how and whether removing copper from the body through a process called “chelation” affects tumor angiogenesis. It has been studied in advanced and refractory cancers, including metastatic chondrosarcoma, mesothelioma and kidney and liver cancers.
Several chelating agents work to reduce copper levels:
- Tetrathiomolybdate (TM)
- D-penicillamine (DPA or D-PEN)
- Tetraethylenetetraamine (TETA or trientine)
- Nitrilotriacetic acid (NTA)
8-Hydroxyquinolines chelate copper and other metals.
Some chelators have been taken off the market due to side effects.
Treating the Cancer
Highlighted Video
BCCT advisor Brian Bouch, MD, discusses copper chelation for cancer care.
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Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action
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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
Brain Cancer
- D-Pen has been effective in removing copper and reducing ceruloplasmin levels in phase 2 trial in glioblastoma.
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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- No notable improvements in time to progression when TM was combined with irinotecan, 5-fluorouracil, and leucovorin (IFL) in patients with advanced metastatic colorectal cancer; no increase in toxicity or interference with effects of irinotecan, 5-fluorouracil, and leucovorin
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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- TM was well tolerated and consistently depleted copper in patients with advanced kidney cancer; clinical activity was limited to stable disease for a median of 34.5 weeks.
Prostate Cancer
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- Slower PSA progression in a small clinical trial of TM with prostate cancer patients, 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 Advanced or Metastatic Cancer
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- Copper chelation with TM promoted tumor dormancy and helped prevent relapse in both laboratory studies and in people with advanced cancer.
- 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.
- Anti-angiogenic activity (blocking the formation of new blood vessels) with TM in animals, with a favorable toxicity profile in preliminary clinical studies
- Anticancer effects in prostate cancer cells from pyrrolidine dithiocarbamate (PDTC) but not TM
- D-Pen inhibits gliosarcoma and melanoma tumor growth in animals and is an effective antiangiogenic agent (blocking the formation of new blood vessels) in gliomas in rats.
- Colon cancer:
- Antitumor activity in human colon cancer cells grafted onto mice
- Affected proliferation, survival and migration in colorectal cancer cells with BRAF mutation, a gene mutation which may increase the growth and spread of cancer cells. Copper chelation also decreased the cloning potential of BRAF cells otherwise resistant to drugs targeting the BRAF mutation
- Melon extracts, especially melon peel aqueous extract, showed copper-chelating properties in lab studies.
- Copper chelators plus iron chelators combined with DHA and 5-FU in colorectal cancer cells overcame drug resistance through increased cell death (apoptosis).
Reducing Risk
Reducing the risk of developing cancer or the risk of recurrence
- Copper chelation with TM reduced relapse.
Optimizing Your Terrain
Creating an environment within your body that does not support cancer development, growth or spread
- Anti-inflammatory
- Improved immune pathway response in animals
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
- Parmar & Kazcor treatment plans
BCCT is aware of several reputable integrative oncologists seeing positive responses to using copper chelation in patients with advanced solid tumors.
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.
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