Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models.

ABSTRACT: The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2. Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated cancer cell growth and proliferation, increased cell death, and increased oxidative stress, which col

SUBMITTER: Schulte ML 

PROVIDER: S-EPMC5803339 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature