HO-1 drives autophagy as a mechanism of resistance against HER2-targeted therapies.

ABSTRACT: PURPOSE:Targeted therapies have resulted in major advances in the treatment of HER2-positive breast cancers. Despite this, up to 70% of patients will develop resistance to treatment within 2 years and new strategies for targeting resistant disease are needed. METHODS:To identify potential resistance mechanisms, we used the mouse MMTV-NIC-PTEN+/- spontaneous model of HER2-positive breast cancer and the pan-HER family kinase inhibitor sapatinib. Vehicle and sapatinib-treated tumors were evaluated by immunohistochemistry and proteomic analysis. In vitro studies were carried out to define the role of heme oxygenase 1 (HO-1) and autophagy in resistance to sapatinib and lapatinib, another pan-HER family kinase inhibitor. RESULTS:Treatment of tumor-bearing MMTV-NIC-PTEN+/- mice with sapatinib res

SUBMITTER: Tracey N 

PROVIDER: S-EPMC6997276 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature