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.
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