Faculty, Staff and Student Publications
Publication Date
2-17-2023
Journal
iScience
Abstract
Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence of resistance to AVA therapy resulted in a decreased metabolic conversion of pyruvate to lactate as assessed by hyperpolarized magnetic resonance spectroscopy and demonstrated robust antitumor effects with a survival advantage. Given the increasing population of patients receiving AVA therapy, these findings justify further development of GLSi in AVA resistance.
Keywords
Oncology, Cellular physiology, Cancer
DOI
10.1016/j.isci.2023.106020
PMID
36824283
PMCID
PMC9941132
PubMedCentral® Posted Date
January 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Obstetrics and Gynecology Commons, Oncology Commons