title: Therapeutic implications of tumor interstitial acidification.
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.
authors.affiliation: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden.
authors.forename: Iryna
authors.initials: I
authors.lastname: Kolosenko
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
authors.affiliation: Sprint Bioscience AB, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Viklund
authors.affiliation: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden. Electronic address: angelo.de-milito@ki.se.
authors.forename: Angelo
authors.initials: A
authors.lastname: De Milito
mesh_terms: D000143:Acids / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy
chemical_list: D000143:Acids
keywords: Cancer therapy; Drug design; Ion trapping; Tumor acidosis; Tumor metabolism