Exploring Biologic Correlates of Cancer-Related Fatigue in Men With Prostate Cancer: Cell Damage Pathways and Oxidative Stress

Abstract

The pathobiology of cancer-related fatigue (CRF) remains elusive, hindering the development of targeted treatments. Radiation therapy (RT), a common treatment for men with prostate cancer, induces cell damage through the generation of free radicals and oxidative stress. We hypothesized that disruption in cellular responses to this surge of nonphysiological oxidative stress might contribute to CRF in men with prostate cancer treated with RT. We evaluated the potential role of three cell damage pathways (apoptosis, autophagy, necrosis) and oxidative stress in CRF in men with prostate cancer receiving RT. Fatigue was measured by the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Gene expression was measured in whole blood using RT² profiler™ PCR arrays. Data were collected at two time points: either baseline or Day 1 of treatment (T1) and completion of treatment (T2). Participants were grouped into either the fatigued or nonfatigued phenotype at T2 using the recommended FACT-F cut-off score for clinical significance. We observed significant upregulation of seven genes related to three cell damage pathways in the fatigued group from T1 to T2 and no significant changes in the nonfatigued group. We also observed significant downregulation of two genes related to oxidative stress in the fatigued group compared to the nonfatigued group at T2. These collective results provide preliminary evidence that cell damage might be upregulated in the CRF phenotype. Validation of these findings using a larger and more diverse sample is warranted.

Keywords

fatigue prostate cancer radiation

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