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Assessment of the Metabolic Profile of Primary Leukemia Cells
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Metabolic Reprogramming During Multidrug Resistance in Leukemias

Raphael Silveira Vidal1, Julia Quarti1,2, Mariana Figueiredo Rodrigues

  • 1Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Frontiers in Oncology
|April 21, 2018
PubMed

Insights

Cancer drug resistance, known as multidrug resistance (MDR), is linked to metabolic changes. Targeting cancer cell metabolism, especially glycolytic enzymes like glyceraldehyde-3-phosphate dehydrogenase, may overcome MDR.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Cancer treatment has improved with targeted therapies, but multidrug resistance (MDR) remains a significant challenge, hindering treatment success.
  • The MDR phenotype confers resistance to structurally diverse drugs with different mechanisms of action.
  • Emerging evidence links the acquisition of drug resistance to significant metabolic reprogramming in cancer cells.

Purpose of the Study:

  • To review the relationship between metabolic reprogramming and the MDR phenotype in cancer.
  • To explore the potential of targeting cancer cell metabolism as a strategy to overcome drug resistance.
  • To highlight the non-metabolic functions of glycolytic enzymes, particularly glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the context of MDR.

Main Methods:

  • Literature review focusing on studies investigating metabolic alterations in multidrug-resistant cancer cells.
  • Analysis of research on the non-metabolic roles of enzymes within the glycolytic pathway.
  • Emphasis on the specific functions of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in drug resistance.

Main Results:

  • Metabolic reprogramming, including increased gene expression, active transport, and altered redox status, is associated with increased energy demands in resistant cells.
  • The precise role of metabolic shifts in the induction versus maintenance of MDR is still under investigation.
  • Glycolytic enzymes, such as GAPDH, possess non-metabolic functions that may contribute to the MDR phenotype.

Conclusions:

  • Metabolism represents a promising therapeutic target for overcoming or preventing multidrug resistance in cancer.
  • Understanding the multifaceted roles of glycolytic enzymes, especially GAPDH, is crucial for developing novel anti-cancer strategies.
  • Targeting metabolic pathways and associated non-metabolic functions could provide new avenues to improve cancer treatment outcomes.
Keywords:
glyceraldehyde-3-phosphate dehydrogenaseglycolysisleukemiamultidrug resistancereactive oxygen species

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