Therapeutic implications of tumor interstitial acidification

Iryna Kolosenko, Sofia Avnet, Nicola Baldini, Jenny Viklund, Angelo De Milito

Research output: Contribution to journalArticlepeer-review

Abstract

Interstitial acidification is a hallmark of solid tumor tissues resulting from the combination of different factors, including cellular buffering systems, defective tissue perfusion and high rates of cellular metabolism. Besides contributing to tumor pathogenesis and promoting tumor progression, tumor acidosis constitutes an important intrinsic and extrinsic mechanism modulating therapy sensitivity and drug resistance. In fact, pharmacological properties of anticancer drugs can be affected not only by tissue structure and organization but also by the distribution of the interstitial tumor pH. The acidic tumor environment is believed to create a chemical barrier that limits the effects and activity of many anticancer drugs. In this review article we will discuss the general protumorigenic effects of acidosis, the role of tumor acidosis in the modulation of therapeutic efficacy and potential strategies to overcome pH-dependent therapy-resistance.

Original languageEnglish
Pages (from-to)119-133
Number of pages15
JournalSeminars in Cancer Biology
Volume43
DOIs
Publication statusPublished - 2017

Keywords

  • Cancer therapy
  • Drug design
  • Ion trapping
  • Tumor acidosis
  • Tumor metabolism

ASJC Scopus subject areas

  • Cancer Research

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