MTORC1-Inhibition Potentiating Metabolic Block by Tyrosine Kinase Inhibitor Ponatinib in Multiple Myeloma.

ABSTRACT: Studies in targeting metabolism in cancer cells have shown the flexibility of cells in reprogramming their pathways away from a given metabolic block. Such behavior prompts a combination drug approach in targeting cancer metabolism, as a single compound may not address the tumor intractability. Overall, mammalian target of rapamycin complex 1 (mTORC1) signaling has been implicated as enabling metabolic escape in the case of a glycolysis block. From a library of compounds, the tyrosine kinase inhibitor ponatinib was screened to provide optimal reduction in metabolic activity in the production of adenosine triphosphate (ATP), pyruvate, and lactate for multiple myeloma cells; however, these cells displayed increasing levels of oxidative phosphorylation (OXPHOS), enabling them to continue gene

SUBMITTER: Nazim UM 

PROVIDER: S-EPMC9179535 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature