ArticleCancer research2012
Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 105 citations in OpenAlex.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Advances in understanding the mechanisms underlying acquired resistance to third-generation tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
- IFITM3-MET interaction drives osimertinib resistance through AKT pathway activation in EGFR-mutant non-small cell lung cancer.Molecular cancer · 2025Article
- *Mechanisms of circular RNA in drug resistance of lung cancer: therapeutic targets, biomarkers, and future research directions.Discover oncology · 2025Review
- New advances in understanding the mechanisms and treatment challenges of ALK-targeted therapy resistance in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse.Cold Spring Harbor perspectives in medicine · 2024Review
- Receptor tyrosine kinase inhibitors in cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Preclinical assessment of combination therapy of EGFR tyrosine kinase inhibitors in a highly heterogeneous tumor model.Oncogene · 2022Article
- Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds.BMC pulmonary medicine · 2021Article
- Selective Inhibitor of the c-Met Receptor Tyrosine Kinase in Advanced Hepatocellular Carcinoma: No Beneficial Effect With the Use of Tivantinib?Frontiers in immunology · 2021Review
- Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC.Cancer research · 2019Article
- Noise-precision tradeoff in predicting combinations of mutations and drugs.PLoS computational biology · 2019Article
- Prediction of ultra-high-order antibiotic combinations based on pairwise interactions.PLoS computational biology · 2019Article
- Exploiting vulnerabilities in cancer signalling networks to combat targeted therapy resistance.Essays in biochemistry · 2018Review
- Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance.Oncotarget · 2018Review
- Clinical management of epidermal growth factor receptor mutation-positive non-small cell lung cancer patients after progression on previous epidermal growth factor receptor tyrosine kinase inhibitors: the necessity of repeated molecular analysis.Translational lung cancer research · 2017Review
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Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Tyrosine kinase inhibitors (TKI) that target the EGF receptor (EGFR) are effective in most non-small cell lung carcinoma (NSCLC) patients whose tumors harbor activating EGFR kinase domain mutations. Unfortunately, acquired resistance eventually emerges in these chronically treated cancers. Two of the most common mechanisms of acquired resistance to TKIs seen clinically are the acquisition of a secondary "gatekeeper" T790M EGFR mutation that increases the affinity of mutant EGFR for ATP and activation of MET to offset the loss of EGFR signaling. Although up to one-third of patient tumors resistant to reversible EGFR TKIs harbor concurrent T790M mutation and MET amplification, potential therapies for these tumors have not been modeled in vivo. In this study, we developed a preclinical platform to evaluate potential therapies by generating transgenic mouse lung cancer models expressing EGFR-mutant Del19-T790M or L858R-T790M, each with concurrent MET overexpression. We found that monotherapy targeting EGFR or MET alone did not produce significant tumor regression. In contrast, combination therapies targeting EGFR and MET simultaneously were highly efficacious against EGFR TKI-resistant tumors codriven by Del19-T790M or L858R-T790M and MET. Our findings therefore provide an in vivo model of intrinsic resistance to reversible TKIs and offer preclinical proof-of-principle that combination targeting of EGFR and MET may benefit patients with NSCLC.
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What OpenQuestion holds
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.