Peroxiredoxins in Colorectal Cancer: Predictive Biomarkers of Radiation Response and Therapeutic Targets to Increase Radiation Sensitivity?

Colorectal cancer (CRC) is the third most common cancer in the Western world, with one-third of cases located in the rectum. Preoperative radiotherapy is the standard of care for many patients with rectal cancer but has a highly variable response rate. The ability to predict response would be of great clinical utility. The response of cells to ionizing radiation is known to involve immediate damage to biomolecules and more sustained disruption of redox homeostasis leading to cell death. The peroxiredoxins are an important group of thiol-dependent antioxidants involved in protecting cells from oxidative stress and regulating signaling pathways involved in cellular responses to oxidative stress. All six human peroxiredoxins have shown increased expression in CRC and may be associated with clinicopathological features and tumor response to ionizing radiation. Peroxiredoxins can act as markers of oxidative stress in various biological systems but they have not been investigated in this capacity in CRC. As such, there is currently insufficient evidence to support the role of peroxiredoxins as clinical biomarkers, but it is an area worthy of investigation. Future research should focus on the in vivo response of rectal cancer to radiotherapy and the redox status of peroxiredoxins in rectal cancer cells, in order to predict response to radiotherapy. The peroxiredoxin system is also a potential therapeutic target for CRC.