ArticleClinical and translational medicine2021
Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Strategies for Targeting Mitochondria in the Treatment of Breast Cancer.ACS pharmacology & translational science · 2026Review
- Ivabradine induces RAD51 degradation, potentiating PARP inhibitor efficacy in non-germline BRCA pathogenic variant triple-negative breast cancer.Journal of translational medicine · 2025Article
- The Splice Variant of the NCOR2 Gene BQ323636.1 Modulates ACSL4 Expression to Enhance Fatty Acid Metabolism and Support of Tumor Growth in Breast Cancer.International journal of molecular sciences · 2025Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.Cell reports · 2023Article
- Construction of a prediction model for prognosis of bladder cancer based on the expression of ion channel-related genes.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Article
- Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data.Frontiers in immunology · 2022Article
- Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.Clinical and translational medicine · 2021Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a small molecule HCN channel-blocker, is FDA-approved for clinical use as a heart rate-reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient-derived tumour xenograft models established from triple-negative breast cancer (TNBC) tissues, with no evident side-effects on the mice. Transcriptome-wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER-stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER-stress, in part due to disturbed Ca
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Registered trials
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