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Curr Pharm Des. 2018;24(44):5268-5295. doi: 10.2174/1381612825666190122163832.

Emerging Therapeutic Targets in Oncologic Photodynamic Therapy.

Author information

1
"Victor Babes" National Institute of Pathology, Bucharest, Romania.
2
Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
3
CQFM-Centro de Fisica Molecular and IN-Institute for Nanosciences and Nanotechnologies and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal.
4
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
5
"Horia Hulubei" National Institute for Physics and Nuclear Engineering, Extreme Light Infrastructure - Nuclear Physics ELI-NP, Bucharest-Magurele, Romania.
6
Research Centre of the University of Bucharest, Bucharest, Romania.
7
Molecular Biology Genetics & Program, Faculty of Engineering & Natural Sciences, Sabanci University, Istanbul, Turkey.
8
Dokumar, Istanbul, Turkey.
9
Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
10
Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain.
11
Department of Biochemistry, Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC and Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.

Abstract

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 translation of PDT to clinic and the development of new therapeutic strategies aimed at improving PDT.

KEYWORDS:

Cancer; inflammation; oxidative stress; photodynamic therapy; reactive oxygen species; redox signalling; transcription factor NRF2.

[Indexed for MEDLINE]

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