Targeting vacuolar H+-ATPases as a new strategy against cancer

Cancer Res. 2007 Nov 15;67(22):10627-30. doi: 10.1158/0008-5472.CAN-07-1805.


Growing evidence suggests a key role of tumor acidic microenvironment in cancer development, progression, and metastasis. As a consequence, the need for compounds that specifically target the mechanism(s) responsible for the low pH of tumors is increasing. Among the key regulators of the tumor acidic microenvironment, vacuolar H(+)-ATPases (V-ATPases) play an important role. These proteins cover a number of functions in a variety of normal as well as tumor cells, in which they pump ions across the membranes. We discuss here some recent results showing that a molecular inhibition of V-ATPases by small interfering RNA in vivo as well as a pharmacologic inhibition through proton pump inhibitors led to tumor cytotoxicity and marked inhibition of human tumor growth in xenograft models. These results propose V-ATPases as a key target for new strategies in cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Membrane / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Ions / chemistry
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms / metabolism*
  • Neoplasms / therapy*
  • Proton-Translocating ATPases / chemistry*
  • Reactive Oxygen Species
  • Vacuoles / metabolism*


  • Antineoplastic Agents
  • Ions
  • Reactive Oxygen Species
  • Proton-Translocating ATPases