Pathobiology and Therapeutic Implications of Tumor Acidosis

Jenny Viklund, Sofia Avnet, Angelo De Milito

Research output: Contribution to journalReview articlepeer-review

Abstract

Drug resistance and therapeutic failure are important causes of disease relapse and progression and may be considered as major obstacles preventing cure of cancer patients. Tumors use a large number of molecular, biochemical and cellular mechanisms to evade chemotherapy and targeted therapy. Important determinants of drug efficacy are the intrinsic pharmacological characteristics of drugs which may be largely affected by the tumor physiology. One feature of solid tumors is the acidic extracellular pH, resulting from metabolic shift and increased metabolic rates combined with low tissue perfusion due to defective vasculature. Besides its role in tumor pathobiology promoting tumor growth and metastasis, the acidic tumor environment creates a chemical barrier for many anticancer drugs, thus limiting their activity. The content of this review will be focused on the pathobiology of tumor acidosis and on its role in therapeutic resistance.

Original languageEnglish
Pages (from-to)2827-2845
Number of pages19
JournalCurrent Medicinal Chemistry
Volume24
Issue number26
DOIs
Publication statusPublished - 2017

Keywords

  • Cancer
  • drug resistance
  • ion trapping
  • permeability
  • pKa.
  • tumor acidosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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