Inhibiting ERK dimerization ameliorates BRAF-driven anaplastic thyroid cancer.

ABSTRACT:

Background

RAS-to-ERK signaling is crucial for the onset and progression of advanced thyroid carcinoma, and blocking ERK dimerization provides a therapeutic benefit in several human carcinomas. Here we analyzed the effects of DEL-22379, a relatively specific ERK dimerization inhibitor, on the activation of the RAS-to-ERK signaling cascade and on tumor-related processes in vitro and in vivo.

Methods

We used a panel of four human anaplastic thyroid carcinoma (ATC) cell lines harboring BRAF or RAS mutations to analyze ERK dynamics and tumor-specific characteristics. We also assessed the impact of DEL-22379 on the transcriptional landscape of ATC cell lines using RNA-sequencing and evaluated its therapeutic efficacy in an orthotopic mouse model of ATC.

Results

DEL-22379 i

SUBMITTER: Zaballos MA 

PROVIDER: S-EPMC9440884 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature