Anti-tumor activity and acquired resistance mechanism of Dovitinib (TKI258) in RET rearranged lung adenocarcinoma

ABSTRACT: RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore anti-tumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell cycle arrest at G0/G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong anti-tumor effect of dovitinib was observed in LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to g

ORGANISM(S): Homo sapiens

SUBMITTER: Kyoung-Ho Pyo 

PROVIDER: E-GEOD-69226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress