Relationship Between Mitochondrial Dysfunction and Fatique in Cancer Patients Following External Beam Radiation Therapy
Fatigue is a common early and chronic adverse effect of radiation but its correlates and
prevalence are poorly understood. Over 40% of cancer patients receive radiation therapy
during the management of their disease. While external beam intensity modulated radiation
therapy (EBRT/IMRT) successfully increases disease-free survival rates and life expectancy,
ionizing radiation leads to increased treatment-related adverse effects including fatigue.
Multidimensional causes and mechanisms of cancer-related fatigue remain unclear, and early
biomarkers prognostic for radiation-induced fatigue have not been identified.
There is evidence that an increase in reactive oxygen species (ROS) formation will cause
cellular damage resulting in dysfunction to mitochondria. ROS are considered one of the
major direct causes of ionizing radiation-induced damage, resulting in a number of adverse
effects (e.g. fatigue, nausea, vomiting, diarrhea, peripheral neuropathy, and cognitive
function impairment) that reduce the efficacy of treatment. Mitochondrial dysfunction is
involved in all clinical conditions including fatigue which are associated with the
deficient energy metabolism of oxidative phosphorylation. Mitochondria are vulnerable to ROS
which are generated endogenously (e.g. mitochondrial superoxide) and exogenously (e.g.
ionizing radiation, inflammation). Once mitochondrial proteins are damaged, the affinity of
substrates or enzymes is decreased resulting in mitochondrial dysfunction including reduced
ATP production, increased ROS generation, and initiated apoptosis signaling. While
mitochondrial dysfunction has been implicated in a variety of clinical fatigue states, the
physiological pathways and pathophysiological mechanisms are complicated and remain unclear.
The primary purpose of this study is to explore the relationships between mitochondrial
dysfunction and fatigue in prostate cancer patients receiving EBRT. Specific aims include:
(1) identify mitochondrial-related gene expression profile changes over time; (2) quantify
the severity of perceived fatigue before, during and at the end of radiation therapy; (3)
determine possible pathways and early biomarkers of mitochondrial dysfunction related to
fatigue in patients with prostate cancer receiving EBR. Blood samples and self-administrated
questionnaires are collected at baseline, midpoint and the end of EBRT. Human mitochondrial
PCR array will be utilized to identify differential regulation of genes involved in
mitochondrial dysfunction at the different time points compared with gene expression from
the baseline samples.
Time Perspective: Prospective
Leorey N Saligan, C.R.N.P.
National Institute of Nursing Research (NINR)
United States: Federal Government
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