Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.

ABSTRACT:

Purpose

In a head and neck squamous cell carcinoma (HNSCC) "window of opportunity" clinical trial, we reported that trametinib reduced MEK-Erk1/2 activation and resulted in tumor responses in a subset of patients. Here, we investigated resistance to trametinib and molecular correlates in HNSCC cell lines and patient samples.

Experimental design

HNSCC cell lines were treated with trametinib to generate resistant lines. Candidate bypass pathways were assessed using immunoblotting, CRISPR knockout, and survival assays. Effectiveness of combined trametinib and verteporfin targeting was evaluated. Patient-derived xenografts (PDXs) from responder patients were treated with trametinib and resistant tumors were analyzed. Window trial clinical samples were subjected to whole-exome an

SUBMITTER: Mudianto T 

PROVIDER: S-EPMC8046740 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature