Copper promotes the formation of blood vessels, including those that supply tumors. Depleting copper can deprive the tumor of a blood supply of oxygen and nutrients. 

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See commentary regarding use by professionals in How do experts use copper chelation?

Modes of action

Copper levels in blood plasma are significantly increased in neoplasias in the stomach, large intestine and lungs.1Scanni A, Licciardello L, Trovato M, Tomirotti M, Biraghi M. Serum copper and ceruloplasmin levels in patients with neoplasias localized in the stomach, large intestine or lung. Tumori. 1977;63(2):175–180. As disease progresses, copper levels further increase, and they decline with remission.2Scanni A, Tomirotti M et al. Variations in serum copper and ceruloplasmin levels in advanced gastrointestinal cancer treated with polychemotherapy. Tumori. 1979;65(3):331–338.

Intratumoral copper levels influence PD-L1 expression in cancer cells, and copper regulates key signaling pathways mediating PD-L1-driven cancer immune evasion. Copper chelators inhibited phosphorylation of STAT3 and EGFR and promoted ubiquitin-mediated degradation of PD-L1.3Voli F, Valli E et al. Intratumoral copper modulates pd-l1 expression and influences tumor immune evasion. Cancer Research. 2020 Oct 1;80(19):4129-4144.

The inflammatory response induces copper uptake through an IL-17-STEAP4-XIAP axis, promoting colon tumorigenesis.4Liao Y, Zhao J et al. Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis. Nature Communications. 2020 Feb 14;11(1):900.

Preclinical evidence

The strongest preclinical evidence for each cancer type is presented here; clinical evidence is in How can copper chelation help you? What the research says ›

Improving treatment outcomes

Zinc-carnosine metallodrug network nanoparticles, a dual metabolism inhibitor, exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models.5Lei L, Nan B et al. Zinc-carnosine metallodrug network as dual metabolism inhibitor overcoming metabolic reprogramming for efficient cancer therapy. Nano Letters. 2023 Apr 12;23(7):2659-2668.

Cancer as a whole
  • A nanohybrid comprising 3-azidopropylamine, 4-ethynylaniline, and N-aminoethyl-N’-benzoylthiourea (BTU) co-modified gold nanoparticles (AuNPs) caused copper deficiency, inhibiting vascularization and tumor migration and leading to a high survival rate of tumor-bearing mice after application.6Yin T, Yang T et al. Intelligent gold nanoparticles for malignant tumor treatment via spontaneous copper manipulation and on-demand photothermal therapy based on copper induced click chemistry. Acta Biomaterialia. 2023 Aug;166:485-495.
  • A copper chelate of Schiff base, copper (II)-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (CuPHMBA), kills both the drug-resistant and sensitive cancer cell types irrespective of their drug resistance phenotype.7Banerjee K, Basu S et al. Induction of intrinsic and extrinsic apoptosis through oxidative stress in drug-resistant cancer by a newly synthesized Schiff base copper chelate. Free Radical Research. 2016;50(4):426-46.
  • Copper chelators decreased tumor growth of human or murine cells transformed by BRAF(V600E) or engineered to be resistant to BRAF inhibition.8Brady DC, Crowe MS et al. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 2014 May 22;509(7501):492-6. 
  • The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis.9Ishida S, Andreux P, Poitry-Yamate C, Auwerx J, Hanahan D. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proceedings of the National Academy of Sciences of the USA. 2013 Nov 26;110(48):19507-12.
  • Copper-lowering agents reduced hCtr1-associated resistance to cisplatin in a variety of cancer cells.10Liang ZD, Long Y et al. Mechanistic basis for overcoming platinum resistance using copper chelating agents. Molecular Cancer Therapies. 2012 Nov;11(11):2483-94.
  • Adding the copper chelator ATN-224 to herpes simplex virus-derived oncolytic viruses (oHSV) to treat tumor growth increased serum stability of oHSV and greatly enhanced its replication and antitumor efficacy.11Yoo JY, Pradarelli J et al. Copper chelation enhances antitumor efficacy and systemic delivery of oncolytic HSV. Clinical Cancer Research. 2012 Sep 15;18(18):4931-41.
Brain cancer
Breast cancer
  • Copper deficiency impaired tumor growth and angiogenesis in an inflammatory breast cancer xenograft and in Her2/neu cancer-prone transgenic mice.14Pan Q, Kleer CG et al. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Research. 2002 Sep 1;62(17):4854-9. 
  • Copper depletion inhibited tumor growth and substantially improved survival of triple-negative breast cancer in mice.15Cui L, Gouw AM et al. Mitochondrial copper depletion suppresses triple-negative bre ast cancer in mice. Nature Biotechnology. 2021 Mar;39(3):357-367.
  • A redox-responsive paclitaxel (PTX) prodrug conjugating PTX with a copper chelator through a disulfide bond generated an enhanced therapeutic outcome toward triple-negative breast cancer.16Hao D, Meng Q et al. A paclitaxel prodrug with copper depletion for combined therapy toward triple-negative breast cancer. ACS Nano. 2023 Jul 11;17(13):12383-12393.
  • Copper chelation restored cytotoxic activity of anthracyclines.17Wiegmans AP, Saunus JM et al. Secreted cellular prion protein binds doxorubicin and correlates with anthracycline resistance in breast cancer. JCI Insight. 2019 Feb 26;5(6):e124092.
Cervical cancer
Colon cancer
  • Copper chelation showed antitumor activity in human colon cancer cells grafted onto mice.19Fatfat M, Merhi RA et al. Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species. BMC Cancer. 2014;14:527.
  • Copper chelation 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.20Baldari S, Di Rocco G et al. Effects of copper chelation on BRAFV600E positive colon carcinoma cells. Cancers (Basel). 2019;11(5):659.
  • The copper chelator elesclomol promotes the degradation of the copper transporter copper-transporting ATPase 1 (ATP7A), which retards the proliferation of colorectal cancer cells.21Gao W, Huang Z et al. Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A. Molecular Oncology. 2021 Dec;15(12):3527-3544.
  • Melon extracts, especially melon peel aqueous extract, showed copper-chelating properties in lab studies.22Rolim PM, Fidelis GP et al. Phenolic profile and antioxidant activity from peels and seeds of melon (Cucumis melo L. var. reticulatus) and their antiproliferative effect in cancer cells. Brazilian Journal of Medical and Biological Research. 2018;51(4):e6069.
  • Copper chelators plus iron chelators combined with DHA and 5-FU in colorectal cancer cells overcame drug resistance through apoptosis.23Yu N, Zhu H et al. Combination of Fe/Cu -chelators and docosahexaenoic acid: an exploration for the treatment of colorectal cancer. Oncotarget. 2017;8(31):51478–51491.
Head and neck cancer
  • Pretreatment with either of 2 copper chelators, cuprizone or bathocuproine sulphonate, significantly increased cisplatin’s sensitivity in squamous cell carcinoma of the head and neck SCCHN), particularly in the context of TMEM16A overexpression.24Vyas A, Duvvuri U, Kiselyov K. Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity. Biochemical Journal. 2019 Dec 19;476(24):3705-3719. 
Leukemia
Liver cancer
  • Copper chelation forestalled hepatocellular tumor cell survival after exposure to hypoxia.26Davis CI, Gu X et al. Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation. Metallomics. 2020 Dec 23;12(12):1995-2008.
Lung cancer
  • Copper chelation therapy inhibited both autophagy and MAPK signaling in BRAFV600E-driven lung adenocarcinoma cells.27Tsang T, Gu X et al. BRAFV600E-driven lung adenocarcinoma requires copper to sustain autophagic signaling and processing. Molecular Cancer Research. 2022 Jul 6;20(7):1096-1107.
  • Curcumin inhibits copper influx and increases uptake of platinum ions in non-small cell lung cancer tumors.28Zhang W, Shi H et al. Curcumin enhances cisplatin sensitivity of human NSCLC cell lines through influencing Cu-Sp1-CTR1 regulatory loop. Phytomedicine. 2018 Sep 15;48:51-61.
Melanoma
  • Casuarictin (CAS), isolated from clove extracts, possessed robust copper chelating ability and inhibited intracellular melanogenesis in mouse melanoma cells.29Goenka S, Ceccoli J, Simon SR. Anti-melanogenic activity of ellagitannin casuarictin in B16F10 mouse melanoma cells. Natural Product Research. 2021 Jun;35(11):1830-1835.
  • The copper chelator 5,6,7,8-tetrahydro-4H-furo[3,2-c]azepine-4-thione (T4FAT), a thioamide derivative, inhibited melanogenesis in mouse melanoma cells.30Okajima S, Hamamoto A et al. Azepine derivative T4FAT, a new copper chelator, inhibits tyrosinase. Biochemical and Biophysical Research Communications. 2019 Jan 29;509(1):209-215. 
  • Tetrathiomolybdate (TM) inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors.31Brady DC, Crowe MS, Greenberg DN, Counter CM. Copper chelation inhibits BRAFV600E-driven melanomagenesis and counters resistance to BRAFV600E and MEK1/2 inhibitors. Cancer Research. 2017 Nov 15;77(22):6240-6252. 
  • D-Pen inhibits melanoma tumor growth in animals.32Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treatment Reviews. 2009;35(1):32–46.
Pancreatic cancer
  • Intracellular copper deprivation induced by CTR1 gene knock-down or systematic copper chelation by tetrathiomolybdate suppressed proliferation and angiogenesis of pancreatic cancer cells.33Geng R, Ke N et al. Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chemico-Biological Interactions. 2023 Sep 1;382:110546. 
Prostate cancer
Thyroid cancer
  • Tetrathiomolybdate (TM) was as or more potent than lenvatinib and sorafenib and enhanced the antineoplastic activity of sorafenib and vemurafenib on papillary thyroid cancer cells, and TM as a maintenance therapy after cessation of vemurafenib reduced tumor volume.35Xu M, Casio M, Range DE, Sosa JA, Counter CM. Copper chelation as targeted therapy in a mouse model of oncogenic BRAF-driven papillary thyroid cancer. Clinical Cancer Research. 2018 Sep 1;24(17):4271-4281. 

Optimizing your body terrain

Copper chelation shows these body terrain impacts in preclinical studies:

  • Antioxidant: Excess copper is a potent oxidant, causing the generation of harmful reactive oxygen species (ROS) in cells. These ROSs are known to drive cancer development and growth.36Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treatment Reviews. 2009;35(1):32–46. 
  • Immune function: Improved immune pathway response in animals37Khan G, Merajver S. Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm. Expert Opinion on Investigational Drugs. 2009;18(4):541–548.
  • Anti-inflammatory effects in animal studies38Brewer GJ. Anticopper therapy against cancer and diseases of inflammation and fibrosis. Drug Discovery Today. 2005;10(16):1103–1109.

Professional commentary

Naturopathic physician Mark Bricca, ND, MAc, June 11, 2025

Helpful links for professionals

KNOW Oncology ›

A subscription is required; access is free of charge for members of the Society for Integrative Oncology.

Shanbhag VC, Gudekar N et al. Copper metabolism as a unique vulnerability in cancer. Biochimica et Biophysica Acta. Molecular Cell Research. 2021 Feb;1868(2):118893.

Tsang T, Posimo JM et al. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nature Cell Biology. 2020 Apr;22(4):412-424.

Rieber M. Cancer pro-oxidant therapy through copper redox cycling: repurposing disulfiram and tetrathiomolybdate. Current Pharmaceutical Design. 2020;26(35):4461-4466.

Keep reading about copper chelation

Authors

Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, MSN, RN, OCNS Senior Clinical Consultant

Nancy Hepp, MS

past Lead Researcher
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS past Lead Researcher

Reviewers

Silvia G. Corral, MD, is an established family medicine physician with Medical Patient Advocacy in Santa Barbara, California. She has 36 years of experience in her field with special expertise in cancer recovery. Dr. Corral received her medical degree at Stanford University and then interned at the University of California, Los Angeles. She is board certified by the American Board of Family Medicine and member of the American Society of Clinical Oncology.

Silvia G. Corral, MD

Jen Green, ND, FABNO

Naturopathic oncologist and CancerChoices advisor
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Dr. Green is a naturopathic physician who is board-certified in naturopathic oncology (FABNO). Dr. Green is also a cofounder/research director for Knowledge in Integrative Oncology Website, a nonprofit website that harvests up-to-date research in integrative oncology to support evidence-informed decision making. Dr. Green has published scientific articles in journals such as the American Urology Association Update SeriesJournal of Alternative & Complementary Medicine and Natural Medicine Journal.

Jen Green, ND, FABNO Naturopathic oncologist and CancerChoices advisor

Last update: June 26, 2025

Last full literature review: August 2024

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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