Selpercatinib combination with the mitochondria-targeted antioxidant MitoQ effectively suppresses RET-mutant thyroid cancer.

ABSTRACT: Genetic alternation of REarranged during Transfection (RET) that leads to constitutive RET activation is a crucial etiological factor for thyroid cancer. RET is known to regulate mitochondrial processes, although the underlying molecular mechanisms remain unclear. We previously showed that the multi-kinase inhibitors vandetanib and cabozantinib increase the mitochondrial membrane potential (Δψ_m) in RET-mutated thyroid tumor cells and that this effect can be exploited to increase mitochondrial enrichment of Δψ_m-sensitive agents in the tumor cells. In this study, we hypothesized that the RET-selective inhibitor, selpercatinib, can increase Δψ_m and, subsequently, tumor cell uptake of the mitochondria-targeted ubiquinone (MitoQ) to the level to break the mitoch

SUBMITTER: Chen W 

PROVIDER: S-EPMC10879150 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature