Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer.

ABSTRACT:

Background

Targeted therapies for triple-negative breast cancer (TNBC) are limited; however, the epidermal growth factor receptor (EGFR) represents a potential target, as the majority of TNBC express EGFR. The purpose of these studies was to evaluate the effectiveness of two EGFR-targeted antibody-drug conjugates (ADC: ABT-414; ABBV-321) in combination with navitoclax, an antagonist of the anti-apoptotic BCL-2 and BCL-X_L proteins, in order to assess the translational relevance of these combinations for TNBC.

Methods

The pre-clinical efficacy of combined treatments was evaluated in multiple patient-derived xenograft (PDX) models of TNBC. Microscopy-based dynamic BH3 profiling (DBP) was used to assess mitochondrial apoptotic signaling induced by navitoclax and/or AD

SUBMITTER: Zoeller JJ 

PROVIDER: S-EPMC7708921 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature