ArticleNPJ breast cancer2017
Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo.
Article in NPJ breast cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 41 citations in OpenAlex.
- Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).Nature communications · 2020Trial
- Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.Signal transduction and targeted therapy · 2023Review
- The importance of being CAFs (in cancer resistance to targeted therapies).Journal of experimental & clinical cancer research : CR · 2022Review
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Ibrutinib reverses IL-6-induced osimertinib resistance through inhibition of Laminin α5/FAK signaling.Communications biology · 2022Article
- Article
- Article
- Abnormally activated OPN/integrin αVβ3/FAK signalling is responsible for EGFR-TKI resistance in EGFR mutant non-small-cell lung cancer.Journal of hematology & oncology · 2020Article
- Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer.Breast cancer research : BCR · 2020Article
- Fibroblast-tumor cell signaling limits HER2 kinase therapy response via activation of MTOR and antiapoptotic pathways.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages.Nature communications · 2020Article
- Neutralization of BCL-2/XMolecular cancer therapeutics · 2019Article
- Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer.Cancers · 2019Review
- Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment.Molecular cancer · 2019Review
- Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues.Nano letters · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Several lines of evidence suggest that components of the tumor microenvironment, specifically basement membrane and extracellular matrix proteins, influence drug sensitivities. We previously reported differential drug sensitivity of tumor cells localized adjacent to laminin-rich extracellular matrix in three-dimensional tumor spheroid cultures. To evaluate whether differential intra-tumor responses to targeted therapy occur in vivo, we examined the sensitivity of human epidermal growth factor receptor 2-positive tumors to lapatinib using a previously described ductal carcinoma in situ-like model characterized by tumor cell confinement within ductal structures surrounded by an organized basement membrane. Here we show that tumor cells localized to a 'niche' in the outer layer of the intraductal tumors adjacent to myoepithelial cells and basement membrane are resistant to lapatinib. We found that the pro-survival protein BCL2 is selectively induced in the niche-protected tumor cells following lapatinib treatment, and combined inhibition of HER2 and BCL-2/XL enhanced targeting of these residual tumor cells. Elimination of the niche-protected tumor cells was achieved with the HER2 antibody-drug conjugate T-DM1, which delivers a chemotherapeutic payload. Thus, these studies provide evidence that subpopulations of tumor cells within specific microenvironmental niches can adapt to inhibition of critical oncogenic pathways, and furthermore reveal effective strategies to eliminate these resistant subpopulations.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.