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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 3907147, 18 pages
Review Article

The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression

1Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
2Department of Cellular and Molecular Pathology, IRCCS San Raffaele, 00166 Rome, Italy
3Consortium MEBIC, San Raffaele University, 00166 Rome, Italy
4Department of Gynecological-Obstetrical Sciences and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy
5Department of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy

Received 23 July 2015; Accepted 29 September 2015

Academic Editor: Sahdeo Prasad

Copyright © 2016 Marco Tafani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a “physiological” response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progression.