ArticleCell reports2015
Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 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.
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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
187 citing papers in PubMed, 280 citations in OpenAlex.
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- Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex.Cancer discovery · 2017Trial
- Advances in the design and discovery of small-molecule tyrosine kinase inhibitors for breast cancer.RSC advances · 2026Review
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- KDM3A Modulates Trastuzumab Resistance in HER2- Positive Breast Cancer Cells via the PI3K/AKT/ERK Pathway.Biochemical genetics · 2026Article
- Ex vivo drug screening and clustering of bladder cancers for pre-clinical treatment prediction.Communications medicine · 2026Article
- Proteomic approaches for interrogating kinase signaling networks.The Journal of investigative dermatology · 2026Article
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- BDDN: bayesian dynamic differential network analysis in cancer proteomics.BMC bioinformatics · 2026Article
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Kinome Reprogramming of G2/M Kinases and Repression of MYCN Contribute to Superior Efficacy of Lorlatinib in ALK-Driven Neuroblastoma.Molecular cancer therapeutics · 2025Article
- Identifying and exploiting combinatorial synthetic lethality by characterizing adaptive kinome rewiring of EGFRvIII-driven glioblastoma.Acta neuropathologica communications · 2025Article
- Development of cellular models expressing cynomolgus (Frontiers in pharmacology · 2025Article
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.Nature communications · 2024Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
- Kinome-Wide Virtual Screening by Multi-Task Deep Learning.International journal of molecular sciences · 2024Article
- Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.Cell genomics · 2024Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutics that target ERBB2, such as lapatinib, often provide initial clinical benefit, but resistance frequently develops. Adaptive responses leading to lapatinib resistance involve reprogramming of the kinome through reactivation of ERBB2/ERBB3 signaling and transcriptional upregulation and activation of multiple tyrosine kinases. The heterogeneity of induced kinases prevents their targeting by a single kinase inhibitor, underscoring the challenge of predicting effective kinase inhibitor combination therapies. We hypothesized that, to make the tumor response to single kinase inhibitors durable, the adaptive kinome response itself must be inhibited. Genetic and chemical inhibition of BET bromodomain chromatin readers suppresses transcription of many lapatinib-induced kinases involved in resistance, including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream SRC/FAK signaling and AKT reactivation. Combining inhibitors of kinases and chromatin readers prevents kinome adaptation by blocking transcription, generating a durable response to lapatinib, and overcoming the dilemma of heterogeneity in the adaptive response.
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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.