ArticlePloS one2015
Autophagy Protects from Trastuzumab-Induced Cytotoxicity in HER2 Overexpressing Breast Tumor Spheroids.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Proteomic Characterization of a 3D HER2+ Breast Cancer Model Reveals the Role of Mitochondrial Complex I in Acquired Resistance to Trastuzumab.International journal of molecular sciences · 2024Article
- 3D tumor spheroids: morphological alterations a yardstick to anti-cancer drug response.In vitro models · 2023Review
- Autophagy: A challengeable paradox in cancer treatment.Cancer medicine · 2023Review
- Generation and Integrated Analysis of Advanced Patient-Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells.Cell death & disease · 2021Article
- Antibody-drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells.Scientific reports · 2021Article
- Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.Cell death & disease · 2021Article
- Review
- Review
- Her2-Targeted Therapy Induces Autophagy in Esophageal Adenocarcinoma Cells.International journal of molecular sciences · 2018Article
- Autophagy flux inhibition augments gastric cancer resistance to the anti-human epidermal growth factor receptor 2 antibody trastuzumab.Oncology letters · 2018Article
- Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2Journal of experimental & clinical cancer research : CR · 2017Article
- Drug delivery in a tumour cord model: a computational simulation.Royal Society open science · 2017Article
- EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.Cancers · 2017Review
- The synthetic peptide CIGB-300 modulates CK2-dependent signaling pathways affecting the survival and chemoresistance of non-small cell lung cancer cell lines.Cancer cell international · 2017Article
- Article
- Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer.Cancer medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multicellular tumor spheroids represent a 3D in vitro model that mimics solid tumor essential properties including assembly and development of extracellular matrix and nutrient, oxygen and proliferation gradients. In the present study, we analyze the impact of 3D spatial organization of HER2-overexpressing breast cancer cells on the response to Trastuzumab. We cultured human mammary adenocarcinoma cell lines as spheroids with the hanging drop method and we observed a gradient of proliferating, quiescent, hypoxic, apoptotic and autophagic cells towards the inner core. This 3D organization decreased Trastuzumab sensitivity of HER2 over-expressing cells compared to monolayer cell cultures. We did not observe apoptosis induced by Trastuzumab but found cell arrest in G0/G1 phase. Moreover, the treatment downregulated the basal apoptosis only found in tumor spheroids, by eliciting protective autophagy. We were able to increase sensitivity to Trastuzumab by autophagy inhibition, thus exposing the interaction between apoptosis and autophagy. We confirmed this result by developing a resistant cell line that was more sensitive to autophagy inhibition than the parental BT474 cells. In summary, the development of Trastuzumab resistance relies on the balance between death and survival mechanisms, characteristic of 3D cell organization. We propose the use of spheroids to further improve the understanding of Trastuzumab antitumor activity and overcome resistance.
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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.