Research ArticleCancer

A recombinant human protein targeting HER2 overcomes drug resistance in HER2-positive breast cancer

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Science Translational Medicine  23 Jan 2019:
Vol. 11, Issue 476, eaav1620
DOI: 10.1126/scitranslmed.aav1620

A protein treatment for resistant cancer

The human epidermal growth factor receptor 2 (HER2) is present in many breast cancers and can be targeted using drugs such as trastuzumab. Unfortunately, tumors develop resistance to HER2 inhibitors, and additional options are needed to overcome it. Yang et al. discovered that a protein called peptidase D can target HER2 and the epidermal growth factor receptor (EGFR), which helps drive resistance. The authors designed an enzymatically inactive form of peptidase D, which blocks HER2 and EGFR but is otherwise inactive. They showed that it works by a different mechanism than preexisting drugs targeting these receptors and thus helps to overcome drug resistance.

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