ArticleInternational journal of molecular sciences2021
Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Cancer-associated fibroblast-derived protein S100-A11 influences the response to anti-HER2 therapies in HER2-positive breast cancer.Neoplasia (New York, N.Y.) · 2026Article
- Computer-Aided Drug Design Across Breast Cancer Subtypes: Methods, Applications and Translational Outlook.International journal of molecular sciences · 2025Review
- Tumor microenvironment response to neoadjuvant therapy in breast cancer: insights from single-cell and spatial omics.Medical oncology (Northwood, London, England) · 2025Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- Effect of HER2 expression status on the prognosis of patients with HROncology letters · 2023Article
- Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.Signal transduction and targeted therapy · 2023Review
- Review
- A ceRNA network-mediated over-expression of cuproptosis-related gene SLC31A1 correlates with poor prognosis and positive immune infiltration in breast cancer.Frontiers in medicine · 2023Article
- Cancer-associated fibroblasts: The chief architect in the tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- Secretome analysis of breast cancer cells to identify potential target proteins ofFrontiers in cell and developmental biology · 2023Article
- [Pharmaceuticals (Basel, Switzerland) · 2022Article
- Decoding the byssus fabrication by spatiotemporal secretome analysis of scallop foot.Computational and structural biotechnology journal · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
The combination of trastuzumab plus pertuzumab plus docetaxel as a first-line therapy in patients with HER2-positive metastatic breast cancer has provided significant clinical benefits compared to trastuzumab plus docetaxel alone. However, despite the therapeutic success of existing therapies targeting HER2, tumours invariably relapse. Therefore, there is an urgent need to improve our understanding of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy. It is well known that the tumour microenvironment (TME) has a significant impact on cancer behaviour. Cancer-associated fibroblasts (CAFs) are essential components of the tumour stroma that have been linked to acquired therapeutic resistance and poor prognosis in breast cancer. For this reason, it would be of interest to identify novel biomarkers in the tumour stroma that could emerge as therapeutic targets for the modulation of resistant phenotypes. Conditioned medium experiments carried out in our laboratory with CAFs derived from HER2-positive patients showed a significant capacity to promote resistance to trastuzumab plus pertuzumab therapies in two HER2-positive breast cancer cell lines (BCCLs), even in the presence of docetaxel. In order to elucidate the components of the CAF-conditioned medium that may be relevant in the promotion of BCCL resistance, we implemented a multiomics strategy to identify cytokines, transcription factors, kinases and miRNAs in the secretome that have specific targets in cancer cells. The combination of cytokine arrays, label-free LC-MS/MS quantification and miRNA analysis to explore the secretome of CAFs under treatment conditions revealed several up- and downregulated candidates. We discuss the potential role of some of the most interesting candidates in generating resistance in HER2-positive breast cancer.
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