Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma.

ABSTRACT:

Background

Rhabdomyosarcoma (RMS) is a paediatric cancer driven either by fusion proteins (e.g., PAX3-FOXO1) or by mutations in key signalling molecules (e.g., RAS or FGFR4). Despite the latter providing opportunities for precision medicine approaches in RMS, there are currently no such treatments implemented in the clinic.

Methods

We evaluated biologic properties and targeting strategies for the FGFR4 V550L activating mutation in RMS559 cells, which have a high allelic fraction of this mutation and are oncogenically dependent on FGFR4 signalling. Signalling and trafficking of FGFR4 V550L were characterised by confocal microscopy and proteomics. Drug effects were determined by live-cell imaging, MTS assay, and in a mouse model.

Results

Among recently developed FGFR4-s

SUBMITTER: Fiorito E 

PROVIDER: S-EPMC9681859 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature