Copper Chelation: Are you a health professional?

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.

Are you a health professional?

This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

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

Tetrathiomolybdate (TM) decreased metastases to lungs, LOX activity, and collagen crosslinking in MDA-LM2-luciferase cells in mice.¹²Chan 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.
D-Pen inhibits gliosarcoma tumor growth in animals and is an effective antiangiogenic agent in gliomas in rats.¹³Gupte 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.

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

Ligand-L, a pregnenolone acetate nucleus-based tetrazole derivative that chelates copper, exhibits significant cytotoxic activity against cervical cancer cells, inducing pro-oxidant death.¹⁸Zafar A, Singh S et al. Interaction of C20-substituted derivative of pregnenolone acetate with copper (II) leads to ROS generation, DNA cleavage and apoptosis in cervical cancer cells: Therapeutic potential of copper chelation for cancer treatment. Bioorganic Chemistry. 2019 Jun;87:276-290.

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

D-Penicillamine (D-pen), a copper-chelating agent, in the presence of cupric sulfate resulted in concentration-dependent cytotoxicity.²⁵Gupte A, Mumper RJ. Copper chelation by D-penicillamine generates reactive oxygen species that are cytotoxic to human leukemia and breast cancer cells. Free Radical Biology & Medicine. 2007 Nov 1;43(9):1271-8.

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 BRAF^V600E-driven melanomagenesis and counters resistance to BRAF^V600E 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

Anticancer effects in prostate cancer cells from pyrrolidine dithiocarbamate (PDTC) but not TM³⁴Chen 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.

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

Tetrathiomolybdate is off patent, and insurance virtually never covers it since it is compounded and considered “experimental.” (And there’s been little interest in funding clinical trials using TM in cancer, since it is off patent.)

While the wonderful doctor Mark Rosenberg, MD, uses TM more commonly as part of his treatment for people with active cancer, clinically I and other practitioners I know tend to rely on it primarily for recurrence prevention in higher risk cancers. Once a cancer is in remission, for recurrence to occur a nascent tumor must flip what’s referred to as the “angiogenic switch” to grow any larger than about 2 cubic millimeters, which is the limit for passive diffusion of nutrients and wastes via the extracellular matrix. Half a dozen of the early angiogenic factors, including VEGF and FGF, are highly copper-dependent so we can use TM to selectively chelate copper stored in tissues to limit the supply available for any cancer-related angiogenesis.

Nothing is all good or all bad, and copper is needed in bone marrow for hematopoiesis, for collagen formation, and for proper neurological function. So, in practice I consider using TM in patients at high-risk of cancer recurrence and in those for whom good treatment options do not exist in case of recurrence. Linda Vahdat, MD, has been leading clinical trials using TM in women at high risk of breast cancer relapse (TNBC and stage III cancers), and her findings over the years have consistently been favorable and in alignment with our collective (mine and colleagues’) clinical experience.

TM is compounded into 20 mg capsules, which have a relatively short shelf life after exposure to air (it oxidizes readily and loses potency). The dose gets titrated to control serum ceruloplasmin (Cp), which is the primary copper carrying protein in the blood. Most labs’ lower limit of normal for Cp is about 18mg/dL and, for cancer recurrence prevention, we typically seek to maintain copper in a range between 10 and 15mg/dL. I’ll go lower in higher risk situations, and I am more conservative in folks who have risk for development of cytopenias (such as people who recently completed myelosuppressive chemo, men on long-term ADT). We check Cp at baseline and then monitor Cp and CBC at least every 4 weeks. A typical induction dose, depending on baseline Cp and level of urgency, is 40mg TM orally at the beginning of meals 3x/daily, plus 60mg nightly at bedtime (180mg/daily). Once target Cp is achieved, the dose is adjusted for maintenance, and ideally the therapy is maintained for a total of 3 years at target Cp.

Because TM oxidizes rapidly it is important to source capsules from a compounding pharmacy that understands how to properly store the compound to maintain its potency. I also choose pharmacies that regularly compound TM since this ensures not only their skill in working with it but good turnover in their supply to prevent it from sitting around too long. The only two pharmacies I am currently aware of in the U.S. that meet my criteria are The Prescription Center in West Salem, WI, and Pure Pharmacy in Fishers, IN. Both of these pharmacies do excellent work compounding TM and they hold pharmacy licenses in some different states, which can be helpful depending on where a patient lives.

Adverse effects, in my experience, are rare, and they can include cytopenias in any cell line, development of mild peripheral neuropathy (pins/needles), and leg cramping. All adverse effects, when they arise, are dose-dependent, and typically amenable to dose adjustment and/or supportive strategies. In practice, I’ve not seen people, even those at high recurrence risk, go on to have recurrences after at least a year at target Cp. The challenge, sometimes, is keeping them in durable remission for the first year of treatment, which seems to be the length of time required to adequately “de-copper” any potential tumor microenvironment.

Over the years, I’ve seen some peripheral neuropathy develop in less than 10% of people on long-term TM therapy. Typically, it’s been managed well with dose adjustment to maintain Cp a little higher and, if symptoms are significant, we’ll also bring in the “usual” support for peripheral nerves (Alpha lipoic acid, B6 and B12, acetyl-L-carnitine, etc.). I’ve had one or two people choose to go off TM due to development of peripheral neuropathy, and in these instances the neuropathy has completely resolved within a month or so of cessation of treatment. It is good to watch this, as one would not want significant neuropathy to go unrecognized/treated. It’s a known possible side effect in a minority of TM users, and manageable when it arises, so it’s not something we worry about, just something to be aware of.

Peripheral neuropathy from TM, when it develops, typically takes time—I’ve not seen it arise until after a person has been on TM for a year or more. If a person had peripheral neuropathy, more commonly from cisplatin, oxaliplatin, or some taxane chemotherapies, then I would certainly watch more for this possibility. Peripheral neuropathy, while still possible, is substantially rarer with carboplatin—so while I would still be aware of the possibility, I would be less mindful of it than I would be given use of cis or oxaliplatin.

Of note, there is also good data on TM/copper chelation synergizing with platinum chemo treatments. This is a different use, however, and one needs to take care with lowering copper too much during active chemo treatment, primarily in order not to place too much pressure on marrow hematopoiesis. Concurrent TM use with platinum chemo requires careful attention, as platinum is myelosuppressive and copper reduction can predispose to cytopenias since copper is needed in marrow for blood cell production. So, in the rare instances that I combine these therapies, I simply go easier on dosing and perhaps aim to lower Cp to just below normal, something like 16-18mg/dL, while carefully monitoring for any synergistic stress in the CBC. I don’t do this often but, given data suggesting synergy between platinum and copper reduction, it’s a worthwhile consideration for some patients who are willing to try the treatment for potentially greater therapeutic benefit.

There are nuances to TM therapy in clinical practice, and they’re relatively easy to learn and straightforward to implement. I have found it to be an incredibly valuable resource for people, and I would love to see it utilized much more broadly in integrative oncology.

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

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Laura Pole, MSN, RN, OCNS

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Nancy Hepp, MS

past Lead Researcher

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Silvia G. Corral, MD

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Jen Green, ND, FABNO

Naturopathic oncologist and CancerChoices advisor

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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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Copper Chelation

Are you a health professional?

Modes of action

Preclinical evidence

Improving treatment outcomes

Cancer as a whole

Brain cancer

Breast cancer

Cervical cancer

Colon cancer

Head and neck cancer

Leukemia

Liver cancer

Lung cancer

Melanoma

Pancreatic cancer

Prostate cancer

Thyroid cancer

Optimizing your body terrain

Professional commentary

Helpful links for professionals

Keep reading about copper chelation

Authors

Laura Pole, MSN, RN, OCNS

Nancy Hepp, MS

Reviewers

Silvia G. Corral, MD

Jen Green, ND, FABNO

Learn more

Professionals Hub

How We Rate Therapies

Healing

Health professional comment

References
1	Scanni 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.
2	Scanni 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.
3	Voli 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.
4	Liao 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.
5	Lei 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.
6	Yin 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.
7	Banerjee 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.
8	Brady DC, Crowe MS et al. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 2014 May 22;509(7501):492-6.
9	Ishida 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.
10	Liang ZD, Long Y et al. Mechanistic basis for overcoming platinum resistance using copper chelating agents. Molecular Cancer Therapies. 2012 Nov;11(11):2483-94.
11	Yoo 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.
12	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.
13	Gupte 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.
14	Pan Q, Kleer CG et al. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Research. 2002 Sep 1;62(17):4854-9.
15	Cui L, Gouw AM et al. Mitochondrial copper depletion suppresses triple-negative bre ast cancer in mice. Nature Biotechnology. 2021 Mar;39(3):357-367.
16	Hao 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.
17	Wiegmans 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.
18	Zafar A, Singh S et al. Interaction of C20-substituted derivative of pregnenolone acetate with copper (II) leads to ROS generation, DNA cleavage and apoptosis in cervical cancer cells: Therapeutic potential of copper chelation for cancer treatment. Bioorganic Chemistry. 2019 Jun;87:276-290.
19	Fatfat 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.
20	Baldari S, Di Rocco G et al. Effects of copper chelation on BRAFV600E positive colon carcinoma cells. Cancers (Basel). 2019;11(5):659.
21	Gao 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.
22	Rolim 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.
23	Yu 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.
24	Vyas 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.
25	Gupte A, Mumper RJ. Copper chelation by D-penicillamine generates reactive oxygen species that are cytotoxic to human leukemia and breast cancer cells. Free Radical Biology & Medicine. 2007 Nov 1;43(9):1271-8.
26	Davis CI, Gu X et al. Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation. Metallomics. 2020 Dec 23;12(12):1995-2008.
27	Tsang 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.
28	Zhang 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.
29	Goenka 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.
30	Okajima 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.
31	Brady DC, Crowe MS, Greenberg DN, Counter CM. Copper chelation inhibits BRAF^V600E-driven melanomagenesis and counters resistance to BRAF^V600E and MEK1/2 inhibitors. Cancer Research. 2017 Nov 15;77(22):6240-6252.
32, 36	Gupte 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.
33	Geng 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.
34	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.
35	Xu 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.
37	Khan G, Merajver S. Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm. Expert Opinion on Investigational Drugs. 2009;18(4):541–548.
38	Brewer GJ. Anticopper therapy against cancer and diseases of inflammation and fibrosis. Drug Discovery Today. 2005;10(16):1103–1109.