Reactive oxygen species in cancer

Abstract

Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.

Keywords::

• Oxidative stress
• reactive oxygen species
• cancer
• signal transduction

Acknowledgements

The authors would like to thank Heike Döppler for critical reading of the manuscript.

Declaration of interest: Research in the Storz laboratory is supported by grants from the Mayo Clinic SPORE for Pancreatic Cancer (P50 CA102701), the Mayo Clinic Breast Cancer SPORE (CA116201-03DR4), an AACR-PANCAN Career development grant (08-20-25-STOR), a R21 from the NCI (CA135102) as well as a Bankhead-Coley grant (FLA07BN-08) from the Florida Department of Health. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the review.

This paper was first published online on Early Online on 23 March 2010.