| Autor: |
Mannan A; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia., Germon ZP; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia., Chamberlain J; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.; John Hunter Children's Hospital, New Lambton Heights, NSW 2308, Australia., Sillar JR; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.; Calvary Mater Hospital, Waratah, NSW 2298, Australia., Nixon B; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.; Reproductive Science Group, College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308, Australia., Dun MD; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia. |
| Abstrakt: |
Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL. |
