| First Author | Tilio M | Year | 2016 |
| Journal | Cancer Lett | Volume | 381 |
| Issue | 1 | Pages | 76-84 |
| PubMed ID | 27475932 | Mgi Jnum | J:234986 |
| Mgi Id | MGI:5792593 | Doi | 10.1016/j.canlet.2016.07.028 |
| Citation | Tilio M, et al. (2016) Irreversible inhibition of Delta16HER2 is necessary to suppress Delta16HER2-positive breast carcinomas resistant to Lapatinib. Cancer Lett 381(1):76-84 |
| abstractText | HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Delta16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration promoting aggressive metastatic breast cancer. Consistently, mice transgenic for the human Delta16HER2 isoform (Delta16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. The present study provides preclinical evidence that Delta16HER2 expression confers de novo resistance to standard anti-HER2-therapies such as Lapatinib and acquired resistance to the selective Src inhibitor Saracatinib in breast cancer. Of note, Dacomitinib, an irreversible small molecule pan-HER inhibitor, was able to completely suppress Delta16HER2-driven breast carcinogenesis. Thus, only Dacomitinib may offer benefit in this molecularly defined patient subset by irreversibly inhibiting Delta16HER2 activation. |
