The redox biology network in cancer pathophysiology and therapeutics

• Published in: Redox Biology
• Main Authors: Manda G., Isvoranu G., Comanescu M.V., Manea A., Debelec Butuner B., Korkmaz K.S.
• Other Authors: Ege Üniversitesi
• Format: Review
• Language: English
• Published: Elsevier B.V. 2015
• Subjects: Bystander and abscopal effects; Cancer; Photodynamic therapy; Radiotherapy; Redox signaling; Tumor niche; sami
• Online Access: https://hdl.handle.net/11454/16952; https://doi.org/10.1016/j.redox.2015.06.014

PubMed ID: 26122399 The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the hypoxia map in the tumor niche, along with the adjoining and systemic effects of oxidative stress-based therapies. © 2015 The Authors. BM1203/EU-ROS E05/2014 European Social Fund, ESF European Cooperation in Science and Technology POSDRU141531 Gina Manda, Adrian Manea, Bilge Debelec Butuner and Kemal Sami Korkmaz were supported by the European Cooperation in Science and Technology (COST Action BM1203/EU-ROS ); Gheorghita Isvoranu was supported by the Sectorial Operational Program Human Resources Development (SOPHRD), financed by the European Social Fund and the Romanian Government under the Contract no. POSDRU141531 the work of Maria Victoria Comanescu was supported by the Romanian National Agency for Research and Innovation , under the Program Capacities, Romania-CERN (Grant E05/2014 ). --