Ivermectin Inhibits Estrogen Receptor and HER2 Pathways in Endocrine-Resistant Breast Cancer
Researchers at Chulalongkorn University found that ivermectin significantly suppressed estrogen-induced proliferation and downregulated ER, HER2, and TGF-β pathway markers in endocrine-resistant breast cancer cells, suggesting potential as a repurposed agent to overcome hormonal therapy resistance.
By Sanare Lab · August 6, 2026 · 5 min read
Key Takeaway
A 2026 study from Chulalongkorn University (Thailand), published in PLOS ONE, found that ivermectin — an antiparasitic drug — suppressed estrogen-induced proliferation in ER-positive (estrogen receptor-positive) breast cancer cells and downregulated key resistance markers including ER (estrogen receptor), HER2 (human epidermal growth factor receptor 2), and components of the TGF-β (transforming growth factor beta) signaling pathway. The findings suggest ivermectin may help overcome endocrine resistance — a major challenge in treating hormone-sensitive breast cancer. This is preclinical cell-culture research; ivermectin is not approved for breast cancer treatment.
Endocrine resistance is one of the most significant clinical challenges in treating ER-positive (estrogen receptor-positive) breast cancer, which accounts for approximately 70–80% of all breast cancer cases. While drugs like tamoxifen and aromatase inhibitors are effective initially, many patients eventually develop resistance, leading to disease progression. Identifying agents that can prevent or reverse this resistance is a major research priority.
A study published April 30, 2026, in the open-access journal PLOS ONE by Rujimongkon K and colleagues from the Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, investigated ivermectin's effects on ER-positive and endocrine-resistant breast cancer cells, building on prior work showing ivermectin inhibited breast cancer proliferation via Wnt signaling.
Table of Contents
- Background: Endocrine Resistance in Breast Cancer
- Key Findings
- Mechanism of Action
- Limitations and Context
- Frequently Asked Questions
- Shop Sanare Lab
- References
Background: Endocrine Resistance in Breast Cancer
ER-positive breast cancer cells rely on estrogen signaling to grow. Standard treatments — tamoxifen (a selective estrogen receptor modulator) and aromatase inhibitors — block this signaling. However, cancer cells can develop resistance through multiple mechanisms, including upregulation of HER2 (human epidermal growth factor receptor 2) and activation of the TGF-β (transforming growth factor beta) pathway, which promote cell survival and invasion independent of estrogen.
The authors' previous research had shown that ivermectin inhibited breast cancer cell proliferation and invasion primarily through modulation of the Wnt signaling pathway. This new study extended that work to specifically examine ivermectin's effects in the context of endocrine resistance.
Key Findings
| Target / Pathway | Effect of Ivermectin | Clinical Relevance |
|---|---|---|
| Estrogen-induced proliferation | Significantly suppressed | Blocks estrogen-driven tumor growth |
| ER (estrogen receptor) | Downregulated | Reduces hormone-driven signaling |
| HER2 (human epidermal growth factor receptor 2) | Downregulated | HER2 overexpression drives endocrine resistance |
| ERK (downstream of HER2/TGF-β) | Markedly reduced | ERK promotes cell survival and proliferation |
| pSMAD2 (phosphorylated SMAD2, TGF-β pathway) | Decreased | Reduces TGF-β-driven invasion |
| SMAD4 (favorable prognosis marker) | Maintained | Preserves tumor-suppressive signaling |
Notably, the study found that combining ivermectin with tamoxifen enhanced antiproliferative effects in endocrine-resistant breast cancer cells — a finding with potential clinical implications for patients who have developed resistance to standard hormonal therapy.
Mechanism of Action
The study identified a multi-pathway mechanism for ivermectin's activity in endocrine-resistant breast cancer:
- ER suppression: Ivermectin downregulated the estrogen receptor itself, reducing the cancer cell's ability to respond to estrogen stimulation.
- HER2 downregulation: HER2 overexpression is a key driver of endocrine resistance. By reducing HER2 levels, ivermectin may help restore sensitivity to hormonal therapies.
- TGF-β pathway inhibition: Ivermectin reduced phosphorylated SMAD2 (pSMAD2), a downstream effector of TGF-β signaling linked to cancer invasion and metastasis, while maintaining SMAD4 — a factor associated with favorable prognosis in endocrine resistance.
- ERK reduction: ERK (extracellular signal-regulated kinase) is a downstream effector of both HER2 and TGF-β signaling. Its reduction by ivermectin further suppresses pro-survival signaling in resistant cells.
Limitations and Context
This is an in vitro (cell culture) study. The findings have not been validated in animal models or human clinical trials for breast cancer. The study used specific cell lines that may not represent the full diversity of ER-positive and endocrine-resistant breast cancers. Ivermectin's pharmacokinetics in humans — including achievable concentrations at tumor sites — would need to be established before clinical translation. No human clinical trials of ivermectin for breast cancer have been completed to date.
For background, see our guide to how ivermectin works.
We cover this in more depth in our article on ivermectin cancer protocols and dosing.
For the fuller picture, read our deep dive into ivermectin and cancer immunotherapy.
You can map out a weight-based schedule using our dosage calculator.
For background, see our guide to the ivermectin immunotherapy trial (NCT05318469).
Frequently Asked Questions
What is endocrine resistance in breast cancer?
Endocrine resistance occurs when ER-positive (estrogen receptor-positive) breast cancer cells stop responding to hormonal therapies like tamoxifen or aromatase inhibitors. This can happen through multiple mechanisms, including upregulation of HER2 (human epidermal growth factor receptor 2) and activation of alternative survival pathways like TGF-β (transforming growth factor beta). It is a major clinical challenge because it leads to disease progression despite treatment.
What pathways did ivermectin target in this study?
Ivermectin downregulated the estrogen receptor (ER) and HER2 (human epidermal growth factor receptor 2), reduced ERK (extracellular signal-regulated kinase) activity, and decreased phosphorylated SMAD2 (pSMAD2) — a component of the TGF-β (transforming growth factor beta) pathway linked to cancer invasion. It also maintained SMAD4, a factor associated with favorable prognosis in endocrine resistance.
Did ivermectin enhance tamoxifen's effects?
Yes. Preliminary results in the study indicated that combining ivermectin with tamoxifen enhanced antiproliferative effects in endocrine-resistant breast cancer cells. This suggests ivermectin may have potential as a combination partner with standard hormonal therapies, though this requires further validation in animal models and clinical trials before any conclusions can be drawn.
Is ivermectin approved for breast cancer treatment?
No. Ivermectin is approved only for antiparasitic indications. Its use in cancer treatment is investigational and not supported by completed human clinical trials. Patients with breast cancer should not use ivermectin as a cancer treatment outside of a supervised clinical trial. Always consult a qualified oncologist.
Thai scientists tested ivermectin — an antiparasitic drug — on breast cancer cells that had stopped responding to standard hormonal therapy (a problem called endocrine resistance). They found that ivermectin switched off several proteins that help cancer cells survive and grow despite hormonal treatment, including the estrogen receptor (ER), HER2 (a growth-promoting protein), and components of the TGF-β pathway (which drives cancer invasion). When combined with tamoxifen (a standard breast cancer drug), ivermectin further reduced cancer cell growth. This is early-stage laboratory research only; ivermectin is not approved for breast cancer and has not been tested in human patients for this purpose.
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References
1. Rujimongkon K, Adchariyasakulchai P, Boonyaratsewee C, Horpratraporn K, Ketchart W. Ivermectin inhibits ER, HER2, and TGF-β pathways in ER-positive and endocrine-resistant breast cancer cells. PLoS One. 2026 Apr 30;21(4):e0348260. doi: 10.1371/journal.pone.0348260. PMCID: PMC13132456. PubMed PMID: 42060658
Medical Disclaimer
This article is for educational and informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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Science-based health education team reviewing published research on repurposed drugs, integrative oncology, and evidence-based protocols.