ArticleCell reports2014
Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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
48 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.Molecular oncology · 2025Article
- Combined inhibition of KRASNature communications · 2024Article
- Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse.Cold Spring Harbor perspectives in medicine · 2024Review
- Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor.Cell chemical biology · 2023Article
- Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer.Cancer discovery · 2023Article
- Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development.Cold Spring Harbor perspectives in medicine · 2021Review
- AKAP13 couples GPCR signaling to mTORC1 inhibition.PLoS genetics · 2021Article
- Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic ResponseCancer discovery · 2021Article
- VPS33B suppresses lung adenocarcinoma metastasis and chemoresistance to cisplatin.Genes & diseases · 2021Article
- Simultaneous silencing Aurora-A and UHRF1 inhibits colorectal cancer cell growth through regulating expression of DNMT1 and STAT1.International journal of medical sciences · 2021Article
- mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability.Nature communications · 2020Article
- Article
- Review
- Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers.Cancer cell · 2020Article
- Clustering Sparse Data With Feature Correlation With Application to Discover Subtypes in Cancer.IEEE access : practical innovations, open solutions · 2020Article
- Torin2 inhibits the EGFR-TKI resistant Non-Small Lung Cancer cell proliferation through negative feedback regulation of Akt/mTOR signaling.Journal of Cancer · 2020Article
- Paired Box-1 (PAX1) Activates Multiple Phosphatases and Inhibits Kinase Cascades in Cervical Cancer.Scientific reports · 2019Article
- mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer.Oncogene · 2019Article
- Drug-adapted cancer cell lines as preclinical models of acquired resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
Abstract
Patients with EGFR-mutant lung adenocarcinomas (LUADs) who initially respond to first-generation tyrosine kinase inhibitors (TKIs) develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. The addition of rapamycin reversed resistance in vivo. Analysis of afatinib-plus-cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling, including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib plus cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs.
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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.