ArticleFrontiers in oncology2019
Glutamine Metabolism Drives Growth in Advanced Hormone Receptor Positive Breast Cancer.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 74 citations in OpenAlex.
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- Revolutionizing Breast Cancer Treatment: Harnessing Ehrlich Ascites Carcinoma Model, Cancer Metabolism, and Nanotechnology-Enhanced Chemotherapy for Improved Patient Outcomes.Cell biochemistry and biophysics · 2026Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- In Silico Analysis of the Role of Estrogen Signaling in the Expression of Metabolic Genes in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Proposed Comprehensive Methodology Integrated with Explainable Artificial Intelligence for Prediction of Possible Biomarkers in Metabolomics Panel of Plasma Samples for Breast Cancer Detection.Medicina (Kaunas, Lithuania) · 2025Article
- Triple-positive breast cancer: navigating heterogeneity and advancing multimodal therapies for improving patient outcomes.Cancer cell international · 2025Review
- Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer.JCI insight · 2024Article
- A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.Oncogene · 2024Review
- In Vitro MRS of Cells Treated with Trastuzumab at 1.5 Tesla.International journal of molecular sciences · 2024Article
- Metabolomic Rewiring Promotes Endocrine Therapy Resistance in Breast Cancer.Cancer research · 2024Article
- Mitochondrial inhibitors: a new horizon in breast cancer therapy.Frontiers in pharmacology · 2024Review
- Disclosing a metabolic signature of cisplatin resistance in MDA-MB-231 triple-negative breast cancer cells by NMR metabolomics.Cancer cell international · 2023Article
- Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer.Journal of the Endocrine Society · 2023Article
- HPV16 E6 and E7 Oncoproteins Stimulate the Glutamine Pathway Maintaining Cell Proliferation in a SNAT1-Dependent Fashion.Viruses · 2023Article
- M2 macrophage-derived exosomal miR-193b-3p promotes progression and glutamine uptake of pancreatic cancer by targeting TRIM62.Biology direct · 2023Article
- Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.International journal of medical sciences · 2023Article
- The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness.Frontiers in endocrinology · 2023Review
- The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer.Frontiers in endocrinology · 2023Review
- Hormone-Glutamine Metabolism: A Critical Regulatory Axis in Endocrine-Related Cancers.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Dependence on the glutamine pathway is increased in advanced breast cancer cell models and tumors regardless of hormone receptor status or function. While 70% of breast cancers are estrogen receptor positive (ER+) and depend on estrogen signaling for growth, advanced ER+ breast cancers grow independent of estrogen. Cellular changes in amino acids such as glutamine are sensed by the mammalian target of rapamycin (mTOR) complex, mTORC1, which is often deregulated in ER+ advanced breast cancer. Inhibitor of mTOR, such as everolimus, has shown modest clinical activity in ER+ breast cancers when given with an antiestrogen. Here we show that breast cancer cell models that are estrogen independent and antiestrogen resistant are more dependent on glutamine for growth compared with their sensitive parental cell lines. Co-treatment of CB-839, an inhibitor of GLS, an enzyme that converts glutamine to glutamate, and everolimus interrupts the growth of these endocrine resistant xenografts. Using human tumor microarrays, we show that GLS is significantly higher in human breast cancer tumors with increased tumor grade, stage, ER-negative and progesterone receptor (PR) negative status. Moreover, GLS levels were significantly higher in breast tumors from African-American women compared with Caucasian women regardless of ER or PR status. Among patients treated with endocrine therapy, high GLS expression was associated with decreased disease free survival (DFS) from a multivariable model with GLS expression treated as dichotomous. Collectively, these findings suggest a complex biology for glutamine metabolism in driving breast cancer growth. Moreover, targeting GLS and mTOR in advanced breast cancer may be a novel therapeutic approach in advanced ER+ breast cancer.
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Registered trials
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