Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.

ABSTRACT:

Background

Alterations in metabolism are one of the emerging hallmarks of cancer cells and targeting dysregulated cancer metabolism provides a new approach to developing more selective therapeutics. However, insufficient blockade critical metabolic dependencies of cancer allows the development of metabolic bypasses, thus limiting therapeutic benefits.

Methods

A series of head and neck squamous cell carcinoma (HNSCC) cell lines and animal models were used to determine the efficacy of CPI-613 and CB-839 when given alone or in combination. Glutaminase 1 (GLS1) depletion was achieved by lentiviral shRNAs. Cell viability and apoptosis were determined in HNSCC cells cultured in 2D culture dish and SeedEZ™ 3D scaffold. Molecular alterations were examined by Western blotting and imm

SUBMITTER: Lang L 

PROVIDER: S-EPMC8670127 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature