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| Content Provider | PubMed Central |
|---|---|
| Author | Umelo, Ijeoma Amir, Noeparast Chen, Gang Renard, Marleen Geers, Caroline Vansteenkiste, Johan Giron, Philippe Wever, Olivier De Teugels, Erik Jacques, De Grève |
| Copyright Year | 2016 |
| Abstract | Somatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3V855A somatic mutation homologous to the EGFRL858Ractivating mutation. Co-expression of HER3V855A and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations. |
| Related Links | http://dx.doi.org/10.18632/oncotarget.6585 |
| Ending Page | 3083 |
| Page Count | 16 |
| Starting Page | 3068 |
| File Format | |
| ISSN | 19492553 |
| e-ISSN | 19492553 |
| Journal | Oncotarget |
| Issue Number | 3 |
| Volume Number | 7 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2016-01-01 |
| Access Restriction | Open |
| Rights Holder | Impact Journals LLC |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
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