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Journal: Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer. (Pubmed Central) - Jul 23, 2024
Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.
- |||||||||| telaglenastat (CB-839) / Calithera, JHU083 / Johns Hopkins University, AstraZeneca
Review, Journal: Glutaminase - A potential target for cancer treatment. (Pubmed Central) - Jun 28, 2024
Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.
- |||||||||| telaglenastat (CB-839) / Calithera, JHU083 / Johns Hopkins University, AstraZeneca
Alpha-Ketoglutarate is a master regulator of epigenetic reprogramming in pancreatic ductal adenocarcinoma progression (Section 17) - Mar 5, 2024 - Abstract #AACR2024AACR_7092;
Together, these data suggest that decreasing AKG in PDAC distant metastasis cells, through glutamine deprivation or JHU083, leads to chromatin changes that specify less malignant phenotypes, providing a rationale for targeting glutamine metabolism as a therapy for late-stage PDAC. *APF and MM are co-corresponding authors.
- |||||||||| telaglenastat (CB-839) / Calithera, JHU083 / Johns Hopkins University, AstraZeneca, IPN60090 / UT MD Anderson Cancer Center, Ipsen
Co-targeting asparagine and glutamine metabolism is a viable treatment strategy for PI3K/PTEN mutated cervical cancer (Section 12) - Mar 5, 2024 - Abstract #AACR2024AACR_5940;
This study suggests a potential strategy for improving the treatment of PI3K-AKT-altered cervical tumors by targeting glutamine and asparagine metabolism in combination with standard therapies. These treatment strategies are currently being evaluated in vivo using a patient derived xenograft model with PIK3CA E545K mutation as well as an immunocompetent cervical tumor model in mice with PTEN deletion.
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Glutamine blockade and anti-PD1 treatment reprograms the tumor infiltrating myeloid cells in mouse model of soft tissue sarcomas (Exhibit Hall B) - Sep 27, 2023 - Abstract #SITC2023SITC_1181;
3 We used JHU083, a novel prodrug of a glutamine antagonist (6-Diazo-5-oxo-L-norleucine) to rid the TME of glutamine and interrogate its downstream effects on the TIME...Transcriptional changes upon glutamine blockade, especially upregulation of Apoe, a key apolipoprotein implicated in cholesterol transport points towards rewiring of metabolism of the myeloid cells. This hints that the heterogenous metabolome/lipidome might hold clues to the differential responses to glutamine blockade in the myeloid subsets.
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Journal: T cell metabolic reprogramming in acute kidney injury and protection by glutamine blockade. (Pubmed Central) - May 11, 2023
Given a convergent role for glutamine in T cell metabolic pathways and the availability of a relatively safe glutamine antagonist JHU083, effects on AKI were evaluated...In vitro hypoxia demonstrated upregulation of glycolysis-related enzymes. T cells undergo metabolic reprogramming during AKI, and reconstitution of metabolism by targeting T cell glutamine pathway could be a promising novel therapeutic approach.
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ZFTA-RELA fusion aberrantly drives glutamine metabolism in lethal pediatric ependymomas (Section 11; Poster Board #20) - Mar 14, 2023 - Abstract #AACR2023AACR_8689;
Moreover, JHU-083, a specific pharmacologic inhibitor of glutaminase, killed ZFTA-RELAFUS tumor cells in vitro and in vivo. To summarize, our results suggest that the ZFTA-RELA fusion expressing tumor cells exhibit strong glutamine dependence, and targeting it has significant therapeutic relevance.
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Preclinical, Journal: In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma. (Pubmed Central) - Dec 17, 2022
Infusions with [amide-N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth in both immunocompromised and immunocompetent mice. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase.
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