ArticleEBioMedicine2023
Identifying actionable druggable targets for breast cancer: Mendelian randomization and population-based analyses.
Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- New insights into breast cancer therapy: application and mechanisms of novel targeted nano-formulation.International journal of pharmaceutics: X · 2026Review
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- The Role of ULK3 in Cancer Progression: A Pan-Cancer Bioinformatics Analysis Integrated with Experimental Validation in Prostate Cancer.International journal of molecular sciences · 2026Article
- Exploring spinal degenerative diseases therapy targets through druggability genes: a Mendelian randomization study.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Identification ofMolecular medicine reports · 2026Article
- Genetic evidence for causal roles of circulating proteins on breast cancer susceptibility.iScience · 2026Article
- Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.International journal of molecular sciences · 2026Article
- The exploration of immunological landscape and drug targets in chronic rhinosinusitis with nasal polyps.The World Allergy Organization journal · 2026Article
- Elucidating the Potential of E-cadherin Re-expression along with Trichostatin A and Zebularine in Enhancing Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis in Human Breast Adenocarcinoma Cells.Current cancer drug targets · 2026Article
- Anti-breast Cancer Potential ofCurrent cancer drug targets · 2026Article
- Genetic insights into drug targets for alzheimer's disease: integrative multi-omics analysis.Alzheimer's research & therapy · 2025Article
- Integrative mendelian randomization and multi-omics analysis reveal a gut microbiota-metabolite-CXCL10 axis in breast cancer.AMB Express · 2025Article
- Efferocytosis-related signatures identified via Single-cell analysis and machine learning predict TNBC outcomes and immunotherapy response.Scientific reports · 2025Article
- Causal Associations Between 4907 Circulating Proteins and Hyperlipidemia: A Two-Sample Mendelian Randomization Study Based on European Ancestry.Health science reports · 2025Article
- Bioinformatics analysis identifiesTranslational cancer research · 2025Article
- Leveraging genetic data for female breast cancer prevention and therapy: Perspectives from Mendelian randomization.iMetaOmics · 2025Article
- Association of Breast Cancer and Selective Estrogen Receptor Modulators on the Risk of Meningioma: Insights from Mendelian Randomization.Molecular neurobiology · 2025Article
- Association between antidiabetic drug targets and psychiatric disorders.Schizophrenia (Heidelberg, Germany) · 2025Article
- Druggable genome-wide Mendelian randomization integrating GWAS and eQTL/pQTL data identifies targets for lung squamous cell carcinoma.Scientific reports · 2025Article
- Identification of Druggable Targets for Alzheimer's Disease by Analyzing Circulating Inflammatory Proteins With Mendelian Randomization.Brain and behavior · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets using Mendelian randomization (MR) and then validate the candidate drugs using population-based analyses.
methodsWe identified genetic instruments for 1406 actionable targets of approved non-oncological drugs based on gene expression, DNA methylation, and protein expression quantitative trait loci (eQTL, mQTL, and pQTL, respectively). Genome-wide association study (GWAS) summary statistics were obtained from the Breast Cancer Association Consortium (122,977 cases, 105,974 controls). We further conducted a nested case-control study using data retrieved from Swedish registers to validate the candidate drugs that were identified from MR analyses.
findingsWe identified six significant MR associations with gene expression levels (TUBB, MDM2, CSK, ULK3, MC1R and KCNN4) and two significant associations with gene methylation levels across 21 CpG islands (RPS23 and MAPT). Results from the nested case-control study showed that the use of raloxifene (targeting MAPT) was associated with 35% reduced breast cancer risk (odds ratio, OR, 0.65; 95% confidence interval, CI, 0.51-0.83). However, usage of estradiol, tolterodine, and nitrofurantoin (also targeting MAPT) was associated with increased breast cancer risk, with adjusted ORs and 95% CI of 1.10 (1.07-1.13), 1.16 (1.09-1.24), and 1.09 (1.05-1.13), respectively. The effect of raloxifene and nitrofurantoin lost significance in further validation analyses using active-comparator and new-user design.
interpretationThis large-scale MR analysis, combined with population-based validation, identified eight druggable target genes for breast cancer and suggested that raloxifene is an effective chemoprevention against breast cancer.
fundingSwedish Research Council, Cancerfonden, Crafoordska Stiftelsen, Allmänna Sjukhusets i Malmö Stiftelsen för bekämpande av cancer, 111 Project and MAS cancer.
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