ArticleCancers2019
HER2-Targeted Tyrosine Kinase Inhibitors Cause Therapy-Induced-Senescence in Breast Cancer Cells.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 39 citations in OpenAlex.
- KDM3A Modulates Trastuzumab Resistance in HER2- Positive Breast Cancer Cells via the PI3K/AKT/ERK Pathway.Biochemical genetics · 2026Article
- Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.Life (Basel, Switzerland) · 2026Review
- Therapy-induced senescence in breast cancer and cardiovascular disease: a double-edged biological process.Frontiers in cardiovascular medicine · 2026Review
- Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis.Frontiers in pharmacology · 2026Article
- ALYREF-mediated mInternational journal of biological sciences · 2026Article
- Micromapping (μMap) of HER2 Across Human Breast Cancers: Photocatalytic Proximity Labeling Identifies Primary Resistance Mechanisms and Functional Interactors.bioRxiv : the preprint server for biology · 2025Article
- Review
- Review
- Cellular senescence and SASP in tumor progression and therapeutic opportunities.Molecular cancer · 2024Review
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- STAT3 Pathways Contribute to β-HCH Interference with Anticancer Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2024Article
- IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Neratinib stimulates senescence of mammary cancer cells by reducing the levels of SIRT1.Aging · 2024Article
- Dynamic ultrasound molecular-targeted imaging of senescence in evaluation of lapatinib resistance in HER2-positive breast cancer.Cancer medicine · 2023Article
- Exploring the Communication of the SASP: Dynamic, Interactive, and Adaptive Effects on the Microenvironment.International journal of molecular sciences · 2023Review
- Mammaglobin 1 mediates progression of trastuzumab-resistant breast cancer cells through regulation of cyclins and NF-κB.FEBS open bio · 2022Article
- Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cellular Senescence in Normal Mammary Gland and Breast Cancer. Implications for Cancer Therapy.Genes · 2022Review
- Review
- IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Prolonged treatment of HER2 positive breast cancer cells with tyrosine kinase inhibitors (TKIs) leads to the emergence of acquired resistance. However, the effects of continuous TKI exposure on cell fate, and the steps leading to the acquisition of a resistant phenotype are poorly understood. To explore this, we exposed five HER2 positive cells lines to HER2 targeted therapies for periods of up to 4 weeks and examined senescence associated β-galactosidase (SA-β-gal) activity together with additional markers of senescence. We found that lapatinib treatment resulted in phenotypic alterations consistent with a senescent phenotype and strong SA-β-gal activity in HER2-positive cell lines. Lapatinib-induced senescence was associated with elevated levels of p15 and p27 but was not dependent on the expression of p16 or p21. Restoring wild type p53 activity either by transfection or by treatment with APR-246, a molecule which reactivates mutant p53, blocked lapatinib-induced senescence and caused increased cell death. In contrast to lapatinib, SA-β-gal activity was not induced by exposing the cells to trastuzumab as a single agent but co-administration of lapatinib and trastuzumab induced senescence, as did treatment of the cells with the irreversible HER2 TKIs neratinib and afatinib. Neratinib- and afatinib-induced senescence was not reversed by removing the drug whereas lapatinib-induced senescence was reversible. In summary, therapy-induced senescence represents a novel mechanism of action of HER2 targeting agents and may be a potential pathway for the emergence of resistance.
Indexed as
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.