CIC-Mediated Modulation of MAPK Signaling Opposes Receptor Tyrosine Kinase Inhibitor Response in Kinase-Addicted Sarcoma.

ABSTRACT: Kinase fusions have been identified in a growing subset of sarcomas, but a lack of preclinical models has impeded their functional analysis as therapeutic targets in the sarcoma setting. In this study, we generated models of sarcomas bearing kinase fusions and assessed their response to molecularly targeted therapy. Immortalized, untransformed human mesenchymal stem cells (HMSC), a putative cell of origin of sarcomas, were modified using CRISPR-Cas9 to harbor a RET chromosomal translocation (HMSC-RET). In parallel, patient-derived models of RET- and NTRK-rearranged sarcomas were generated. Expression of a RET fusion activated common proliferation and survival pathways and transformed HMSC cells. The HMSC-RET models displayed similar behavior and response to therapy as the patient-derived c

SUBMITTER: Odintsov I 

PROVIDER: S-EPMC8930606 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature