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.
Keywords: Cancer, drug resistance, tumor acidosis, ion trapping, permeability, pKa.
Current Medicinal Chemistry
Title:Pathobiology and Therapeutic Implications of Tumor Acidosis
Volume: 24 Issue: 26
Author(s): Jenny Viklund, Sofia Avnet and Angelo De Milito*
Affiliation:
- Department of Oncology- Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm,Sweden
Keywords: Cancer, drug resistance, tumor acidosis, ion trapping, permeability, pKa.
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.
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Cite this article as:
Viklund Jenny, Avnet Sofia and Milito De Angelo*, Pathobiology and Therapeutic Implications of Tumor Acidosis, Current Medicinal Chemistry 2017; 24 (26) . https://dx.doi.org/10.2174/0929867323666161228142849
DOI https://dx.doi.org/10.2174/0929867323666161228142849 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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