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The potential of minipigs in the development of anti-cancer therapeutics: species comparison and examples of special applications

Mahl, Joerg Andreas and Dincer, Zuhal and Heining, Peter (2016) The potential of minipigs in the development of anti-cancer therapeutics: species comparison and examples of special applications. Toxicologic Pathology, 44 (3). pp. 391-397.

Abstract

Minipigs are increasingly being used as an alternative to dog or monkey in non-clinical safety testing of pharmaceuticals since they share similar anatomical and physiological characteristics in cardiovascular, urinary, integumentary, ocular and digestive systems to humans. Integrative assessment of pharmacodynamic and pharmacokinetic data sets of drug candidates from in silico, in vitro and in vivo investigations form the basis for selecting the most relevant non-rodent species for toxicology studies. Developing anti-cancer therapeutics represents a special challenge for species selection due to their effects on multiple organ systems, especially those with high cell turnover. The toxicological profile of anti-cancer drugs can be associated with steep dose-response curves, especially due to dose-limiting toxicity on the alimentary, hematopoietic and immune systems. Selection of an appropriate species for toxicology studies is of importance to avoid underestimation of the clinical starting dose without benefit for the late-stage cancer patient or overestimation of this dose with a risk of unexpected adverse reactions. Although the minipig has been the preferred species supporting the development of drugs applied topically, it is only rarely used in anti-cancer drug development compared to dog and monkey. In this context we discuss the potential of the minipig in anti-cancer drug development with examples of programs for oral and dermal administration, intravascular application in drug-eluting stents and local chemotherapy (chemoembolization).

Item Type: Article
Keywords: Minipigs, anti-cancer drug development, species selection for non-clinical safety evaluation, minipig models for special applications
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/26487

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