Significance Reactive oxygen species (ROS) are critical to normal cellular function with redox homeostasis achieved by balancing ROS production with removal through detoxification mechanisms. Many of the conventional chemotherapies used to treat colorectal cancer (CRC) derive a proportion of their cytotoxicity from ROS generation and resistance to chemotherapy is associated with elevated detoxification mechanisms. Furthermore, cancer stem cells demonstrate elevated detoxification mechanisms making definitive treatment with existing chemotherapy challenging. In this article we review the roles of ROS in normal and malignant colonic cell biology and how existing and emerging therapies might harness ROS for therapeutic benefit. Recent advances Recent publications have elucidated the contribution of ROS to the cytotoxicity of conventional chemotherapy alongside the emerging approaches of photodynamic therapy (PDT), sonodynamic therapy (SDT) and radiodynamic therapy (RDT) in which ROS are generated in response to excitatory light, sound or X-ray stimuli to promote cancer cell apoptosis. Critical issues The majority of patients with metastatic CRC have a very poor prognosis with 5-year survival of approximately 13% making the need for new or more effective treatments an imperative. Future Directions Modulation of ROS through a combination of new and emerging therapies may improve the efficacy of current chemotherapy providing novel approaches to treat otherwise resistant disease.
Keyphrases
- reactive oxygen species
- cell death
- dna damage
- poor prognosis
- photodynamic therapy
- locally advanced
- long non coding rna
- squamous cell carcinoma
- radiation therapy
- single cell
- cell proliferation
- computed tomography
- high resolution
- magnetic resonance
- mass spectrometry
- cell therapy
- replacement therapy
- current status
- rectal cancer
- ulcerative colitis
- combination therapy