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Related Experiment Videos

Lonidamine in malignant brain tumors.

D Schiffer1, S Sales, R Soffietti

  • 1II Department of Neurology, University of Torino, Italy.

Seminars in Oncology
|April 1, 1991
PubMed
Summary

Lonidamine targets cancer cell energy production by inhibiting hexokinase in malignant gliomas. This metabolic interference may limit tumor growth and enhance treatment efficacy, with manageable side effects.

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Area of Science:

  • Oncology
  • Cancer Metabolism
  • Neuro-oncology

Background:

  • Malignant gliomas and brain metastases present significant therapeutic challenges.
  • Targeting cancer cell metabolism, specifically aerobic glycolysis, offers a promising therapeutic strategy.
  • Lonidamine is a compound known to interfere with cellular energy production.

Purpose of the Study:

  • To investigate the role of lonidamine in targeting metabolic pathways of human malignant gliomas and glioblastoma cell lines.
  • To evaluate lonidamine's potential as a therapeutic agent in primary and secondary brain tumors, including its effects on radio/chemotherapy.
  • To assess the efficacy and safety profile of lonidamine in brain tumor treatment.

Main Methods:

  • In vitro studies on human malignant glioma and glioblastoma cell lines.
  • Analysis of lonidamine's effect on aerobic glycolysis and lactate production.
  • Investigation of lonidamine's impact on cellular energy-dependent processes.
  • Clinical evaluation of lonidamine in combination with radiotherapy and chemotherapy for brain tumors.

Main Results:

  • Lonidamine inhibits mitochondrially-bound hexokinase, decreasing lactate production and aerobic glycolysis in glioma cells.
  • This metabolic inhibition reduces the energetic capacity of glioma cells, potentially limiting growth and recovery.
  • Lonidamine shows limited but clear therapeutic activity in recurrent malignant gliomas and potentiates systemic chemotherapy in brain metastases.
  • Common side effects include myalgias, testicular pain, and ototoxicity, with no significant organ toxicity or myelosuppression observed.

Conclusions:

  • Lonidamine effectively targets the metabolic vulnerability of malignant gliomas by inhibiting hexokinase and aerobic glycolysis.
  • The drug demonstrates potential as an adjunct therapy in managing brain tumors, particularly in recurrent settings and when combined with chemotherapy.
  • Lonidamine presents a manageable side effect profile, making it a viable option for further clinical investigation in neuro-oncology.

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