Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression

Abstract

Cancer is one of the major causes of death in the world and its global burden is expected to continue increasing. In several types of cancers, reactive oxygen species (ROS) have been extensively linked to carcinogenesis and cancer progression. However, studies have reported conflicting evidence regarding the role of ROS in cancer, mostly dependent on the cancer type or the step of the tumorigenic process. We review recent studies describing diverse aspects of the interplay of ROS with cancer in the different stages of cancer progression, with a special focus on their role in carcinogenesis, their importance for cancer cell signaling and their relationship to the most prevalent cancer risk factors.

Introduction

Cancer is a major health and economic world problem, being the first or second leading cause of premature death (among those 30–69 years of age) in 134 countries of the world. Assuming global rates remain unchanged, projections based on population aging and growth estimate that the global cancer burden will increase by more than 60% in 2040 to 29.4 million cases [1]. Importantly, cancer can be attributed to potentially modifiable risk factors [1], underscoring the need to understand the cellular targets of known carcinogenic agents to design therapeutic interventions that could halt the process of cellular transformation.

Oxidative damage is one of the main contributors to DNA mutations and disruptions in the pro-oxidant/ antioxidant balance have been reported in more than 200 clinical disorders, including chronic diseases like neurodegenerative diseases, inflammatory bowel disease and cancer [2]. Although cancer is a multi-factorial disease, a common consequence of exposure to several of the known cancer risk factors is the production of reactive oxygen species (ROS). Oxidative damage to proteins and DNA is likely to be one of the main contributors to the appearance of DNA mutations and, alterations in signaling pathways involved in the promotion of malignancy and ROS, are known to induce mutations in purines, pyrimidines and oxidate chromatin proteins, inducing genomic instability, affecting gene expression and contributing to carcinogenesis and cancer progression [2]. Here, we review recent evidence implicating changes in the oxidative balance in tumor progression and cancer cell signaling and discuss the role of oxidative damage in known cancer risk factors, as well as the implications of targeting ROS for cancer prevention or treatment.