In Vitro Photobehavior of Tyrosine Kinase Inhibitors in Solution and within Skin Cells

Doctoranda: Meryem El Ouardi
Dirigida por: Prof. Miguel Ángel Miranda Alonso y Dra. Inmaculada Andreu Ros

Unidad Mixta de Investigación en Mecanismos Moleculares de las Reacciones Adversas de Fármacos

The new class of targeted therapy introduced in recent decades, tyrosine kinase inhibitors (TKIs), has significantly improved the quality of life and survival rate of cancer patients. However, given the arising dermatological adverse events, it makes sense to investigate the ability of the TKI family to induce photosensitivity reactions.

Currently, the chemistry of photoinduced processes (energy and/or electron transfer, hydrogen abstraction, ROS formation, etc.) occurring within cells is largely unknown, despite its importance in understanding and predicting photosensitivity reactions. To successfully achieve this overarching goal, a multidisciplinary approach was followed in this doctoral thesis, utilizing photophysical techniques combined with photobiological experiments in solution and within skin cells, including both monolayer systems and reconstructed human epidermis, to emulate the topical application of specific TKI molecules.

The overall outcomes successfully identified potential phototoxic TKIs, which becomes crucial for reducing the incidence of photoinduced events associated with these targeted therapies and for preventing treatment discontinuation in cancer patients. Moreover, in numerous cases, discontinuing or replacing the photosensitizing drug may not be a feasible therapeutic option. Therefore, the main preventive measure against adverse reactions considered is protection from direct sunlight exposure using photoprotection or sunscreens alongside anticancer therapy.

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