Insights into gemcitabine resistance and the potential for therapeutic monitoring

Teklab Gebregiworgis, Fatema Bhinderwala, Vinee Purohit, Nina V. Chaika, Pankaj Singh, Robert Powers

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction: Gemcitabine is an important component of pancreatic cancer clinical management. Unfortunately, acquired gemcitabine resistance is widespread and there are limitations to predicting and monitoring therapeutic outcomes. Objective: To investigate the potential of metabolomics to differentiate pancreatic cancer cells that develops resistance or respond to gemcitabine treatment. Results: We applied 1D 1 H and 2D 1 H– 13 C HSQC NMR methods to profile the metabolic signature of pancreatic cancer cells. 13 C 6 -glucose labeling identified 30 key metabolites uniquely altered between wild-type and gemcitabine-resistant cells upon gemcitabine treatment. Gemcitabine resistance was observed to reprogram glucose metabolism and to enhance the pyrimidine synthesis pathway. Myo-inositol, taurine, glycerophosphocholine and creatinine phosphate exhibited a “binary switch” in response to gemcitabine treatment and acquired resistance. Conclusion: Metabolic differences between naïve and resistant pancreatic cancer cells and, accordingly, their unique responses to gemcitabine treatment were revealed, which may be useful in the clinical setting for monitoring a patient’s therapeutic response.

Original languageEnglish (US)
Article number156
JournalMetabolomics
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

gemcitabine
Monitoring
Pancreatic Neoplasms
Cells
Therapeutics
Glucose
Metabolomics
Metabolome
Taurine
Physiologic Monitoring
Inositol
Metabolites
Metabolism
Labeling
Creatinine

Keywords

  • Drug resistance
  • Gemcitabine
  • NMR metabolomics
  • Pancreatic cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Insights into gemcitabine resistance and the potential for therapeutic monitoring. / Gebregiworgis, Teklab; Bhinderwala, Fatema; Purohit, Vinee; Chaika, Nina V.; Singh, Pankaj; Powers, Robert.

In: Metabolomics, Vol. 14, No. 12, 156, 01.12.2018.

Research output: Contribution to journalArticle

Gebregiworgis, Teklab ; Bhinderwala, Fatema ; Purohit, Vinee ; Chaika, Nina V. ; Singh, Pankaj ; Powers, Robert. / Insights into gemcitabine resistance and the potential for therapeutic monitoring. In: Metabolomics. 2018 ; Vol. 14, No. 12.
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