Hydrogen Ion Dynamics of Cancer and a New Molecular, Biochemical and Metabolic Approach to the Etiopathogenesis and Treatment of Brain Malignancies

Int J Mol Sci. 2019 Sep 1;20(17):4278. doi: 10.3390/ijms20174278.

Abstract

The treatment of cancer has been slowly but steadily progressing during the last fifty years. Some tumors with a high mortality in the past are curable nowadays. However, there is one striking exception: glioblastoma multiforme. No real breakthrough has been hitherto achieved with this tumor with ominous prognosis and very short survival. Glioblastomas, being highly glycolytic malignancies are strongly pH-dependent and driven by the sodium hydrogen exchanger 1 (NHE1) and other proton (H+) transporters. Therefore, this is one of those pathologies where the lessons recently learnt from the new pH-centered anticancer paradigm may soon bring a promising change to treatment. This contribution will discuss how the pH-centric molecular, biochemical and metabolic perspective may introduce some urgently needed and integral novel treatments. Such a prospective therapeutic approach for malignant brain tumors is developed here, either to be used alone or in combination with more standard therapies.

Keywords: cellular acidification in gliomas; etiopathogenesis of gliomas; pH, NHE and proton extruders; pH-centric anticancer paradigm; reverting proton reversal; treatment of glioblastoma multiforme.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Glioblastoma / metabolism*
  • Glycolysis
  • Humans
  • Hydrogen-Ion Concentration
  • Protons*
  • Sodium-Hydrogen Exchanger 1 / metabolism

Substances

  • Protons
  • Sodium-Hydrogen Exchanger 1