THE BARRIER FUNCTION OF ORGANOTYPIC NON-MELANOMA SKIN CANCER MODELS

Christian Zoschke

Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Königin-Luise-Str. 14, 14195 Berlin, Germany

Abstract

Non-melanoma skin cancer (NMSC) is the far most frequent cancer in humans with continuously rising incidences worldwide, but the treatment efficacy remains low. This unmet clinical need and the shortcomings of current preclinical drug development ask for the development of predictive NMSC models.

Herein, crucial culture variables of human cell-based organotypic NMSC models were systematically investigated and the influences on the carcinoma stage as well as on the skin barrier function were analyzed. Organotypic NMSC models closely resemble the skin cancer lesions in patients [1]. Impaired stratum corneum lipid formation and the loss of tight junction proteins enabled the penetration of caffeine and high molecular weight nanocarriers into the NMSC models [2]. Insights into drug effects on organotypic NMSC models became feasible by investigating ingenol mebutate gel. Three topical applications caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase release.

The identified reduction in barrier function of organotypic NMSC models compared with normal human skin models lays the foundation for the reliable use of organotypic NMSC models. Finally, I took organotypic NMSC models as an example to propose an integrated test strategy with reduced numbers of animal tests in advanced preclinical drug evaluation [3].

REFERENCES

[1] Zoschke C, et al., 2016. J Control Release 233: 10-8.
[2] Alnasif N, et al., 2014. J Control Release 185c: 45-50.
[3] Zoschke C, et al. 2015. Curr Pharm Des 21: 2784-800.