ArticleScience signaling2016
Coupling an EML4-ALK-centric interactome with RNA interference identifies sensitizers to ALK inhibitors.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Synthesis and Antitumor Activity of 6-(2-Aminobenzo[ACS omega · 2025Article
- Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer.Cell death & disease · 2024Article
- MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling.Molecular cancer therapeutics · 2024Article
- EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries.Molecular oncology · 2023Review
- ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses viaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.Cellular and molecular life sciences : CMLS · 2022Article
- A Polytherapy Strategy Using Vincristine and ALK Inhibitors to Sensitise EML4-ALK-Positive NSCLC.Cancers · 2022Article
- A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC.EMBO molecular medicine · 2022Article
- Phase-separated foci of EML4-ALK facilitate signalling and depend upon an active kinase conformation.EMBO reports · 2021Article
- Current Knowledge about Mechanisms of Drug Resistance against ALK Inhibitors in Non-Small Cell Lung Cancer.Cancers · 2021Review
- Anti-epidermal growth factor vaccine antibodies increase the antitumor activity of kinase inhibitors in ALK and RET rearranged lung cancer cells.Translational oncology · 2021Article
- Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures.Nature communications · 2020Article
- Review
- Urea Cycle Sustains Cellular Energetics upon EGFR Inhibition in EGFR-Mutant NSCLC.Molecular cancer research : MCR · 2019Article
- Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance.EBioMedicine · 2019Article
- Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma.Science signaling · 2018Article
- CAR-T cells and combination therapies: What's next in the immunotherapy revolution?Pharmacological research · 2018Article
- Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.PLoS biology · 2018Article
- Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor tyrosine kinase inhibitors and inherent therapeutic vulnerabilities.Molecular cancer · 2018Review
- The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC).Molecular cancer · 2018Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with lung cancers harboring anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors, but acquired resistance inevitably arises. A better understanding of proximal ALK signaling mechanisms may identify sensitizers to ALK inhibitors that disrupt the balance between prosurvival and proapoptotic effector signals. Using affinity purification coupled with mass spectrometry in an ALK fusion lung cancer cell line (H3122), we generated an ALK signaling network and investigated signaling activity using tyrosine phosphoproteomics. We identified a network of 464 proteins composed of subnetworks with differential response to ALK inhibitors. A small hairpin RNA screen targeting 407 proteins in this network revealed 64 and 9 proteins that when knocked down sensitized cells to crizotinib and alectinib, respectively. Among these, knocking down fibroblast growth factor receptor substrate 2 (FRS2) or coiled-coil and C2 domain-containing protein 1A (CC2D1A), both scaffolding proteins, sensitized multiple ALK fusion cell lines to the ALK inhibitors crizotinib and alectinib. Collectively, our data set provides a resource that enhances our understanding of signaling and drug resistance networks consequent to ALK fusions and identifies potential targets to improve the efficacy of ALK inhibitors in patients.
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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.