Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment.

ABSTRACT:

Background

Central nervous system (CNS) metastases represent a major problem in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer because of the disappointing efficacy of HER2-targeted therapies against brain lesions. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases.

Methods

We treated female nude mice bearing BT474 or MDA-MB-361 brain metastases (n = 9-11 per group) or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histologi

SUBMITTER: Askoxylakis V 

PROVIDER: S-EPMC4862418 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature