Related Experiment Video
Updated: Aug 29, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
GLS1 is a protective factor in patients with ovarian clear cell carcinoma and its expression does not correlate with
Valentino Clemente1, Asumi Hoshino1, Mihir Shetty1
1Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Abstract:
Targeting glutamine metabolism has emerged as a novel therapeutic strategy for several human cancers, including ovarian cancer. The primary target of this approach is the kidney isoform of glutaminase, glutaminase 1 (GLS1), a key enzyme in glutamine metabolism that is overexpressed in several human cancers. A first-in-class inhibitor of GLS1, called CB839 (Telaglenastat), has been investigated in several clinical trials, with promising results. The first clinical trial of CB839 in platinum-resistant ovarian cancer patients is forthcoming. ARID1A-mutated ovarian clear cell carcinoma (OCCC) is a relatively indolent and chemoresistant ovarian cancer histotype. In OCCC-derived cells ARID1A simultaneously drives GLS1 expression and metabolism reprograming. In ARID1A-mutated OCCC-derived mouse models, loss of ARID1A corresponds to GLS1 upregulation and increases sensitivity to GLS1 inhibition. Thus, targeting of GLS1 with CB839 has been suggested as a targeted approach for OCCC patients with tumors harboring ARID1A-mutations. Here, we investigated whether GLS1 is differentially expressed between OCCC patients whose tumors are ARID1A positive and patients whose tumors are ARID1A negative. In clinical specimens of OCCC, we found that GLS1 overexpression was not correlated with ARID1A loss. In addition, GLS1 overexpression was associated with better clinical outcomes. Our findings have implications for human trials using experimental therapeutics targeting GLS1.
Insights
Targeting glutamine metabolism via glutaminase 1 (GLS1) is a novel cancer therapy. This study found GLS1 overexpression in ovarian clear cell carcinoma (OCCC) did not correlate with ARID1A mutations and was linked to better patient outcomes.
Area of Science:
- Oncology
- Metabolic pathways
- Cancer genetics
Background:
- Targeting glutamine metabolism is a promising cancer therapy.
- Glutaminase 1 (GLS1) is a key enzyme in glutamine metabolism, overexpressed in many cancers.
- CB839 (Telaglenastat) is a GLS1 inhibitor investigated in clinical trials for ovarian cancer.
Purpose of the Study:
- To investigate the correlation between GLS1 expression and ARID1A mutation status in ovarian clear cell carcinoma (OCCC).
- To determine if GLS1 overexpression is associated with clinical outcomes in OCCC patients.
Main Methods:
- Analysis of GLS1 expression in clinical OCCC specimens.
- Correlation of GLS1 expression with ARID1A mutation status.
- Association of GLS1 expression with patient clinical outcomes.
Main Results:
- GLS1 overexpression was not correlated with ARID1A loss in OCCC.
- GLS1 overexpression was associated with better clinical outcomes in OCCC patients.
Conclusions:
- The findings suggest that GLS1 expression levels, not ARID1A mutation status, may be a predictive biomarker for GLS1-targeted therapies in OCCC.
- These results have implications for designing future clinical trials targeting GLS1 in ovarian cancer.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation