Metabolomics

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Increased glucose availability sensitizes pancreatic cancer to chemotherapy


ABSTRACT: Pancreatic cancer (Pancreatic Ductal Adenocarcinoma; PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, and therefore, chemotherapy remains the best available systematic treatment. The discovery of safe and available adjuncts that can improve chemotherapeutic efficacy could potentially improve survival outcomes. We show that a hyperglycemic state enhances the efficacy of conventional single- and multi-agent chemotherapies against PDAC. Molecular analyses of tumors exposed to relatively high glucose levels revealed that GCLC (catalytic subunit of glutamate-cysteine ligase), a key regulator of a metabolic pathway, glutathione biosynthesis, is diminished and underlies chemo-sensitization. Inhibition to GCLC phenocopied the effect of an induced hyperglycemic state in mouse models of PDAC, while rescuing the pathway abrogated the anti-tumor effects observed with chemotherapy treatment under high glucose conditions.

INSTRUMENT(S): Gas Chromatography MS - positive

SUBMITTER: Ali Vaziri-Gohar 

PROVIDER: MTBLS6000 | MetaboLights | 2022-10-18

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS6000 Other
FILES Other
a_MTBLS6000_MET_GC-MS_positive__metabolite_profiling.txt Txt
a_MTBLS6000_TFA_GC-MS_positive__metabolite_profiling.txt Txt
files-all.json Other
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