A Preclinical Model for Mutant Human EGFR-driven Lung Adenocarcinoma

Previously described epidermal growth factor receptor- (EGFR) driven tumor mouse models develop diffuse tumors, which are dissimilar to human lung tumor morphology and difficult to measure by CT and MRI scans. Scientists at the National Cancer Institute (NCI) have developed and characterized a genetically engineered mouse (GEM) model of human EGFR-driven tumor model (hEGFR-TL) that recapitulates the discrete lung tumor nodules similar to those found in human lung tumor morphology. Individual tumor nodules can be easily measured by live animal imaging and the nodules can be harvested and isolated from surrounding lung tissue post-treatment, making this a more tractable model for human non-small cell lung adenocarcinoma. The lungs express an EGFR transgene that harbors two mutations ( ‘L858R’ and ‘T790M’) which render the lung tumors resistant to first generation EGFR inhibitors and are useful for evaluating drugs targeting resistant tumors.IC: NCINIH Ref. No.: E-041-2014Advantages: Lung tumor development and response to drugs can be monitored by MRI or CT scanningContain a human EGFR transgene (either TRE-EGFR-L858R or TRE-EGFR-L858R-T790M models are available) and an activating transgene (CCSP-rtTA) to direct expression of mutant EGFR to the Clara cellsApplications: Preclinical in vivo screen of therapeutics targeting tumor kinase inhibitors such as EGFR-mediated lung tumors, and identification of new biomarkers in this pathway &nbs...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research

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ConclusionsThe uptake of [18F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
There are limited data on the clinical efficiency of afatinib in non ‐small cell lung cancer (NSCLC) patients with uncommon epidermal growth factor receptor (EGFR) mutations. Moreover, the efficacy and safety of afatinib in elderly patients with these mutations has not been established. Here, we describe a case of successful treatment of a patient aged>80  years with lung adenocarcinoma positive for the uncommon EGFR L861Q mutation with low‐dose afatinib. An 83‐year‐old woman presented with cough and dyspnea. A chest computed tomography (CT) scan revealed tumors in the left upper lobe, left pleural effusi...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
AbstractPurposePrognostic significance of volumetric18F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cut-off values for risk stratification were assessed.MethodsThirty-nine patients (29 men and 10 women, 71.9 ± 8.3 years) who underwent FDG PET/CT examinations before C-ion RT were retrospectively evaluated. FDG-PET parameters: standardized uptake values (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and ...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
Rationale: Lung cancer is leadning cause of cancer-related mortality. Lobectomy is considered standard therapy for early stage non-small-cell lung cancer (NSCLC). We therefore set out to investigate outcomes in patients who had sublobar resection compared to lobectomy in our tertiraty centre.Methods: We studied patients who had lung cancer resections between 2010 and 2015. We analysed the data of 265 patients who had either lobar or sublobar resection for stage I NSCLC. The review identified differences in the selection of surgical modality as well as the key outcome variables i.e. recurrence and survival.Results: In our c...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Thoracic surgery Source Type: research
Conclusion :18F-FDG PET/CT metabolic parameters combined with clinicopathological data demonstrated moderate diagnostic efficacy in predicting EGFR mutation status and were associated with prognosis in mutant and wild-type EGFR non-small-cell lung cancer, thus providing a reference for individualized targeted molecular therapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We report the first case of an Indian patient with osimertinib resistance, due to C797S mutation. A 52-year-old nonsmoker man was detected to have metastatic lung adenocarcinoma (Stage IV) with EGFR exon 19 deletion and treated with erlotinib. After 12 months of response with erlotinib, he developed resistance because of the development of T790M mutation. He was started on osimertinib, with which he responded for 20 months. A follow-up positron emission tomography scan showed progressive disease. Subsequent liquid biopsy did not detect any mutation. However, rebiopsy of the lung lesion showed additional C797S mutation (in ...
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
Abstract OBJECTIVE: Non-invasive distinction between squamous cell carcinoma and adenocarcinoma subtypes of non-small-cell lung cancer (NSCLC) may be beneficial to patients unfit for invasive diagnostic procedures or when tissue is insufficient for diagnosis. The purpose of our study was to compare the performance of random forest algorithms utilizing CT radiomics and/or semantic features in classifying NSCLC. METHODS: Two thoracic radiologists scored 11 semantic features on CT scans of 106 patients with NSCLC. A set of 115 radiomics features was extracted from the CT scans. Random forest models were develope...
Source: The British Journal of Radiology - Category: Radiology Authors: Tags: Br J Radiol Source Type: research
Conclusion: In view of the poor specificity, the current study calls for reconsideration of the universal recommendation of dedicated brain imaging (in addition to PET/CT scan) among NSCLC patients beyond stage I. PMID: 31116030 [PubMed - as supplied by publisher]
Source: Journal of Comparative Effectiveness Research - Category: General Medicine Tags: J Comp Eff Res Source Type: research
Conclusions: Hypermetabolic changes on DTP 18F-FDG PET showed good correlation with tumor positive expression of PD-L1 and high density of CD8 TILs and PD-1 in tumor immune microenvironment. Furthermore, dSUVmax was an independent predictor of PD-L1 expression in pretreated NSCLC.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Lung Cancer I: Molecular Biomarkers and Molecular Imaging Signatures Source Type: research
Conclusions: 18F-MPG PET/CT imaging could accurately reflect the slight active mutant EGFR kinase-expression changes induced by EGFR-TKIsin a noninvasive way and real timeboth in preclinical and clinical. Cisplatin or Pemetrexed exposure resulted a dose-dependent decreasein active mutant EGFR NSCLCs, which this molecular level interfering on EGFR signal pathway can be also detected by 18F-MPGPET/CT imaging. Therefore,compared with 18F-FDG,18F-MPG PET/CT is a reliable tool in monitoring NSCLCs treatments, because of it is not easily affected by inflammation induced by chemotherapy and other factors. It has great potential i...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Translational Image Guided Source Type: research
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