ArticleCancer research2012
Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment response.
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 22 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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Early detection of treatment futility in patients with metastatic colorectal cancer.Oncotarget · 2022Trial
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- An Agrin-YAP/TAZ Rigidity Sensing Module Drives EGFR-Addicted Lung Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multi-Omics Approaches for Liver Reveal the Thromboprophylaxis Mechanism of Aspirin Eugenol Ester in Rat Thrombosis Model.International journal of molecular sciences · 2024Article
- Precision immunointerception of EGFR-driven tumorigenesis for lung cancer prevention.Frontiers in immunology · 2023Article
- Characterization of the Immune Landscape of EGFR-Mutant NSCLC Identifies CD73/Adenosine Pathway as a Potential Therapeutic Target.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
- Therapeutic Potential of Glutamine Pathway in Lung Cancer.Frontiers in oncology · 2021Review
- Metabolomics study of oral cancers.Metabolomics : Official journal of the Metabolomic Society · 2019Review
- A strategy for early detection of response to chemotherapy drugs based on treatment-related changes in the metabolome.PloS one · 2019Article
- Serum Metabolic Profile Alteration Reveals Response to Platinum-Based Combination Chemotherapy for Lung Cancer: Sensitive Patients Distinguished from Insensitive ones.Scientific reports · 2017Article
- Monitoring for Response to Antineoplastic Drugs: The Potential of a Metabolomic Approach.Metabolites · 2017Review
- Evaluation of 99mTc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC.Oncotarget · 2017Article
- Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.Theranostics · 2017Review
- A serum metabolomic fingerprint of bevacizumab and temsirolimus combination as first-line treatment of metastatic renal cell carcinoma.British journal of cancer · 2015Article
- Bridging tumor genomics to patient outcomes through an integrated patient-derived xenograft platform.Clinical lung cancer · 2015Article
- β-catenin contributes to lung tumor development induced by EGFR mutations.Cancer research · 2014Article
- A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies.Histochemistry and cell biology · 2014Article
- Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Genetic polymorphisms in oxidative stress-related genes are associated with clinical outcome in patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitors.American journal of cancer research · 2014Article
- Altered glutamine metabolism and therapeutic opportunities for lung cancer.Clinical lung cancer · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared with quantitative imaging and histopathology at several time points during tumor progression and treatment. Responses to single-drug treatments were temporary, whereas combination therapy elicited a sustained response. During tumor development, metabolomic signatures indicated a shift to high anabolic activity and suppression of antitumor programs with 11 metabolites consistently present in both lung tissue and blood. Combination drug treatment reversed many of the molecular changes found in tumored lung. Data integration linking cancer signaling networks with metabolic activity identified key pathways such as glutamine and glutathione metabolism that signified response to single or dual treatments. Results from combination drug treatment suggest that metabolic transcriptional control through C-MYC and SREBP, as well as ELK1, NRF1, and NRF2, depends on both EGFR and mTORC1 signaling. Our findings establish the importance of kinetic therapeutic studies in preclinical assessment and provide in vivo evidence that TKI-mediated antiproliferative effects also manifest in specific metabolic regulation.
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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.