ArticleNature communications2024
Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies.Technology in cancer research & treatmentPooled it
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Rethinking bioinformatics in liquid-liquid phase separation: data resources, predictive models, and an event-centric perspective.Briefings in bioinformatics · 2026Review
- Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- Allosteric drugs in biomolecular condensates: ways forward.Drug discovery today · 2026Review
- Optogenetic Translocation to Subcellular Compartments through Regulation of Protein Avidity.ACS synthetic biology · 2026Article
- Prolonged survival with alectinib in a patient with advanced lung adenocarcinoma: a case report and literature review.Translational cancer research · 2026Article
- Low-order assemblies drive oncogenic RTK fusion signaling without condensation.bioRxiv : the preprint server for biology · 2025Article
- Inverse modeling unveils governing law of mechano-chemical dynamics of epithelial migration.PLoS computational biology · 2025Article
- Quantifying cancer- and drug-induced changes in Shannon information capacity of RTK signaling.Scientific reports · 2025Article
- Case Report: Ensartinib as a first-line treatment for SMARCA4-deficient and EML4-ALK non-small cell lung cancer.Frontiers in oncology · 2025Article
- Principles and functions of condensate modifying drugs.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Drug resistance remains a challenge for targeted therapy of cancers driven by EML4-ALK and related fusion oncogenes. EML4-ALK forms cytoplasmic protein condensates, which result from networks of interactions between oncogene and adapter protein multimers. While these assemblies are associated with oncogenic signaling, their role in drug response is unclear. Here, we use optogenetics and live-cell imaging to find that EML4-ALK assemblies suppress transmembrane receptor tyrosine kinase (RTK) signaling by sequestering RTK adapter proteins including GRB2 and SOS1. Furthermore, ALK inhibition, while suppressing oncogenic signaling, simultaneously releases the sequestered adapters and thereby resensitizes RTK signaling. Resensitized RTKs promote rapid and pulsatile ERK reactivation that originates from paracrine ligands shed by dying cells. Reactivated ERK signaling promotes cell survival, which can be counteracted by combination therapies that block paracrine signaling. Our results identify a regulatory role for RTK fusion assemblies and uncover a mechanism of tolerance to 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.