Skip Navigation Links

The Molecular-Genetic Mechanisms Behind Cancer-Related Fatigue

A recent NINR study found evidence that certain genes are significantly associated with more intense fatigue as reported by prostate cancer patients who are undergoing external beam radiation therapy (EBRT). The findings may help researchers develop targeted treatments for patients suffering from cancer-related fatigue (CRF).

Localized EBRT is a standard treatment option for non-metastatic prostate cancer, and the therapy has increased survival rates for patients. However, men undergoing the treatment frequently report CRF, which is associated with negative health outcomes and decreased quality of life. CRF can last for years after patients complete cancer therapy, negatively impacting their daily activities, work, sexuality, and family life.

To take a closer look at the pathways and biomarkers behind CRF, Dr. Leorey Saligan, principal investigator in NINR’s Symptom Biology Unit, and colleagues designed an experiment to look at the association of changes in mitochondria-related gene expression and increasing fatigue in prostate cancer patients receiving EBRT. The researchers used self-report questionnaires and blood samples, which were collected from patients and healthy controls. The researchers hypothesized that EBRT, which induces apoptosis (programmed cell death) in cancer cells, also alters energy production in the mitochondria of non-tumor cells, contributing to the development or worsening of fatigue.

“Mitochondria play a critical role in generating metabolic energy, and they are vulnerable to one of the major causes of radiation-induced damage,” said Dr. Saligan. “This study is the first to explore the relationship between radiation-induced changes in mitochondria-related gene expression and more intense fatigue in prostate cancer patients before, during, and after EBRT.”

The study, featured in Cancer Nursing, found significant increases in self-reported fatigue and changes in mitochondria-related gene expression over time in subjects with non-metastatic prostate cancer compared to matched controls. Eight genes in particular (AIFM2, BCL2, FIS1, IMMP2L, MSTO1, SLC25A23, SLC25A37, SLC25A4) were significantly associated with changes in fatigue scores. The findings suggest that these genes, which are related to mitochondrial function, may play a critical role in the increasing fatigue experienced by prostate cancer patients undergoing EBRT.

“Further research is needed to investigate the role these genes play in cancer-related fatigue and how we may be able to utilize them in targeted therapies,” said Saligan. “We also need to take a closer look at the specific phenotypes of patients who are prone to develop fatigue during cancer treatment.”

To read the abstract, please visit

Arrow Up Back to Top