ArticleScience signaling2019
Systemic analysis of tyrosine kinase signaling reveals a common adaptive response program in a HER2-positive breast cancer.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
- Adaptive Proteomic Changes in Protein Metabolism and Mitochondrial Alterations Associated with Resistance to Trastuzumab and Pertuzumab Therapy in HER2-Positive Breast Cancer.International journal of molecular sciences · 2025Article
- Measurement of Intratumor Heterogeneity and Its Changing Pattern to Predict Response and Recurrence Risk After Neoadjuvant Chemotherapy in Breast Cancer.Current oncology (Toronto, Ont.) · 2025Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Decrypting the potency of anti-cancer therapeutics by using mass spectrometry to quantify post-translational modifications.Cell reports methods · 2023Article
- Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy.Cancers · 2022Article
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer.Cancer discovery · 2022Article
- Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors.Cancers · 2022Article
- KCell research · 2022Article
- Organ-Specific, Fibroblast-Derived Matrix as a Tool for Studying Breast Cancer Metastasis.Cancers · 2021Article
- Apoptosis-inducing anti-HER2 agents operate through oligomerization-induced receptor immobilization.Communications biology · 2021Article
- Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action.Nature communications · 2021Article
- PamgeneAnalyzeR: open and reproducible pipeline for kinase profiling.Bioinformatics (Oxford, England) · 2020Article
- Article
- Maximized quantitative phosphoproteomics allows high confidence dissection of the DNA damage signaling network.Scientific reports · 2020Article
- Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion.The Journal of biological chemistry · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Drug-induced compensatory signaling and subsequent rewiring of the signaling pathways that support cell proliferation and survival promote the development of acquired drug resistance in tumors. Here, we sought to analyze the adaptive kinase response in cancer cells after distinct treatment with agents targeting human epidermal growth factor receptor 2 (HER2), specifically those that induce either only temporary cell cycle arrest or, alternatively, apoptosis in HER2-overexpressing cancers. We compared trastuzumab, ARRY380, the combination thereof, and a biparatopic, HER2-targeted designed ankyrin repeat protein (DARPin; specifically, 6L1G) and quantified the phosphoproteome by isobaric tagging using tandem mass tag liquid chromatography/tandem mass spectrometry (TMT LC-MS/MS). We found a specific signature of persistently phosphorylated tyrosine peptides after the nonapoptotic treatments, which we used to distinguish between different treatment-induced cancer cell fates. Next, we analyzed the activation of serine/threonine and tyrosine kinases after treatment using a bait peptide chip array and predicted the corresponding active kinases. Through a combined system-wide analysis, we identified a common adaptive kinase response program that involved the activation of focal adhesion kinase 1 (FAK1), protein kinase C-δ (PRKCD), and Ephrin (EPH) family receptors. These findings reveal potential targets to prevent adaptive resistance to HER2-targeted therapies.
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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.