Gina Manda*, Mihail Eugen Hinescu, Ionela Victoria Neagoe, Luis Filipe Vieira Ferreira, Rica Boscencu, Paul Vasos, Selma Huveyda Basaga and Antonio Cuadrado Pages 1 - 18 ( 18 )
Background: Reactive oxygen species sustain tumorigenesis and cancer progression through deregulated redox signalling which also sensitizes cancer cells to therapy. Photodynamic therapy (PDT) is a promising anti-cancer therapy based on a provoked singlet oxygen burst, exhibiting a better toxicological profile than chemo-and radiotherapy. Important gaps in the knowledge on underlining molecular mechanisms impede on its translation towards clinical applications.Aims and Methods: The main objective of this review is to critically analyse the knowledge lately gained on therapeutic targets related to redox and inflammatory networks underlining PDT and its outcome in terms of cell death and resistance to therapy. Emerging therapeutic targets and pharmaceutical tools will be documented based on the identified molecular background of PDT. Results: Cellular responses and molecular networks in cancer cells exposed to the PDT-triggered singlet oxygen burst and the associated stresses are analysed using a systems medicine approach, addressing both cell death and repair mechanisms. In the context of immunogenic cell death, therapeutic tools for boosting anti-tumor immunity will be outlined. Finally, the transcription factor NRF2, which is a major coordinator of cytoprotective responses, is presented as a promising pharmacologic target for developing co-therapies designed to increase PDT efficacy. Conclusion: There is an urgent need to perform in-depth molecular investigations in the field of PDT and to correlate them with clinical data through a systems medicine approach for highlighting the complex biological signature of PDT. This will definitely guide clinical translation of PDT to clinic and the development of new therapeutic strategies aimed at improving PDT.
cancer, photodynamic therapy, reactive oxygen species, oxidative stress, redox signalling, transcription factor NRF2, inflammation.
“Victor Babes” National Institute of Pathology, Bucharest, “Victor Babes” National Institute of Pathology, Bucharest, “Victor Babes” National Institute of Pathology, Bucharest, CQFM-Centrode Química-Física Molecular and IN-Institute for Nanosciences and Nanotechnologies and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, “Horia Hulubei” National Institute for Physics and Nuclear Engineering, Extreme Light Infrastructure - Nuclear Physics ELI-NP, Bucharest-Magurele, Molecular Biology Genetics & Bioengineering Program Faculty of Engineering & Natural Sciences, Sabanci University, Istanbul, ”Victor Babes” National Institute of Pathology, Bucharest