Mechanisms of resistance to Photodynamic Therapy

CASAS A; DI VENOSA G; HASAN T; BATLLE A

CURRENT MEDICINAL CHEMISTRY.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2011 vol. 18 p. 2486 - 2515

0929-8673

Abstract: Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light,leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the generalmechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step,an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes andactivation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, celldetachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair ofinduced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vasculardamage and photochemical oxygen consumption may also contribute to the appearance of resistant cells.The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellularlocalization.Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT andchemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy.The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complexand comprises different mechanisms.In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms mostcommonly found in chemo resistant cells.