The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas.<b>Experimental Design:</b> Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC.<b>Results:</b> The use of targeted therapies in patients with <i>EGFR, ERBB2,</i> or <i>BRAF</i> p.V600E mutations, <i>ALK, ROS1</i>, or <i>RET</i> rearrangements, or <i>MET</i> amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver.
Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood.
In contrast, afatinib and neratinib were predicted to be more effective than other inhibitors for the A775_776insYVMA mutation, the most frequent <i>ERBB2</i> mutation in lung cancer.
The variable responses to anti-HER2 therapies in these patients prompt us to examine impact of <i>HER2</i> variants and co-mutations on responses to anti-HER2 treatments in lung cancer.
Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC).
Germline mutations in EGFR and erb-b2 receptor tyrosine kinase 2 (ERBB2) have been previously reported in lung cancers that may be associated with genetic susceptibility to lung cancer.
Other driver biomarkers in lung cancer (point mutations and rearrangements in specific genes including Her2, BRAF, NUT, MET, ROS1, DDR2, FGFR1, KRAS, and PTEN) might potentially provide additional information for clinical decision making.
Therefore, we tested for possible aberrations of the c-erbB-2 gene in the region of the transmembrane domain in surgical specimens of human primary lung cancer from 190 patients, and also examined 24 metastases and 26 specimens of noncancerous portions of the lung of the same patients.
Our data suggest that heterodimers of MET with EGFR, HER2, HER3, or RET have differential roles in tumour development, and they provide new insight into the function of trans-phosphorylated RTKs as heterodimerisation partners of MET in lung cancer with MET amplification.
To investigate the potential role of the c-erbB-2/neu gene in lung cancer metastasis systematically, we introduced the human c-erbB-2/neu gene into very low p185neu-expressing NCI-H460 human non-small cell lung cancer cells and then examined the experimental metastatic potentials among the parental NCI-H460 cells and stable transfectants with increased expression of p185neu.
Given the high prevalence of lung cancer worldwide and the availability of standard and investigational therapies targeting HER2, routine clinical genotyping of lung ADC should include HER2.
To assess antigen reactivity, <sup>89</sup>Zr-DFO-trastuzumab was evaluated using the Lindmo method and tested in PET/CT imaging of mouse models of human epidermal growth factor receptor 2-positive or -negative lung cancer.
The present study involves ligand-based pharmacophore modeling of various kinases, including EGFR (T790 M), cMET, ErbB2, FGFR and ALK, which are well established targets of normal as well resistant lung cancer.
Paraffin-embedded sections from 42 cases with lung carcinoma were stained immunohistochemically using the Avidin-Biotin Horseradish Peroxidase method to search for c-erbB-2 reaction.
Here, we show that the major lung cancer-derived ERBB2 mutants, including the most frequent mutation, A775insYVMA, lead to oncogenic transformation in a cellular assay.
It eases the sample size bottleneck; evaluations on simulated data and lung cancer-specific ERBB2 and MAPK signaling pathways, with varying number of samples, evince the merit in handling high exon to sample size ratio datasets.
Following the identification of HER2-activating events in the most recent lung carcinoma and in circulating tumor cells, we treated the reminiscent metastatic lesions with a lapatinib-based therapy.