ArticleJournal of experimental & clinical cancer research : CR2024
The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. 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.
- Antibody-drug conjugates in breast cancer: redefining targeted therapy.The Journal of clinical investigation · 2026Review
- ML385 increases ferroptosis via inhibiting Nrf2/HO-1 pathway to enhances the sensitivity of MCF-7 TAMR to tamoxifen.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Acidic Tumor Microenvironments and Emerging Therapeutic Strategies for Cancer Therapy.Yonsei medical journal · 2025Review
- Chemosensitization and Molecular Docking Assessment of Dio-NPs on Resistant Breast Cancer Cells to Tamoxifen.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Unlocking the potential of engineered microbes in immunotoxin-based cancer therapy.Frontiers in microbiology · 2025Review
- Reducing Cabozantinib Toxicity in Renal Cell Carcinoma Treatment through Structural Modifications.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- Target screening and optimization of candidate compounds for breast cancer treatment using bioinformatics and computational chemistry approaches.Frontiers in pharmacology · 2025Article
- Innovative payloads for ADCs in cancer treatment: moving beyond the selective delivery of chemotherapy.Therapeutic advances in medical oncology · 2025Review
- Osthole suppresses prostate cancer progression by modulating PRLR and the JAK2/STAT3 signaling axis.Frontiers in oncology · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
backgroundThough tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge in clinic. Signals downstream of prolactin receptor (PRLR) could synergize with ERα in breast cancer progression. However, the potential effect of targeting PRL-PRLR axis combined with tamoxifen has not been thoroughly investigated.
methodsHigh-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression in breast cancer cell and the association of PRLR expression with tamoxifen treatment. Exogenous or PRL overexpression cell models were employed to investigate the role of activated PRLR pathway in mediating tamoxifen insensitivity. Immunotoxin targeting PRLR (N8-PE24) was constructed with splicing-intein technique, and the efficacy of N8-PE24 against breast cancer was evaluated using in vitro and in vivo methods, including analysis of cells growth or apoptosis, 3D spheroids culture, and animal xenografts.
resultsPRLR pathway activated by PRL could significantly decrease sensitivity of ERα-positive breast cancer cells to tamoxifen. Tamoxifen treatment upregulated transcription of PRLR and could induce significant accumulation of PRLR protein in breast cancer cells by alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved by long-term tamoxifen pressure exhibited both upregulated transcription and protein level of PRLR. Immunotoxin N8-PE24 enhanced sensitivity of breast cancer cells to tamoxifen both in vitro and in vivo. In xenograft models, N8-PE24 significantly enhanced the efficacy of tamoxifen and paclitaxel when treating PRLR-positive triple-negative breast cancer.
conclusionsPRL-PRLR axis potentially associates with tamoxifen insensitivity in ERα-positive breast cancer cells. N8-PE24 could inhibit cell growth of the breast cancers and promote drug sensitivity of PRLR-positive breast cancer cells to tamoxifen and paclitaxel. Our study provides a new perspective for targeting PRLR to treat breast cancer.
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