title: Pathobiology and Therapeutic Implications of Tumor Acidosis.
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.
authors.affiliation: Sprint Bioscience, Stockholm. Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Viklund
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna. Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.affiliation: Department of Oncology- Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm. Sweden.
authors.forename: Angelo
authors.initials: A
authors.lastname: De Milito
mesh_terms: D000138:Acidosis / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; drug resistance; ion trapping; pKa.; permeability; tumor acidosis