Abstract # 3192 Sex as a biological variable in cancer-related fatigue

Abstract

While fatigue is one of the mostly commonly reported side effects of cancer therapy, there is significant variability in intensity and persistence of this symptom. Understanding the factors accounting for this variation may provide insight into mechanisms underlying fatigue. An often overlooked issue is the possible influence of sex differences. The few studies that have been conducted employed patient-reported outcome variables. While a number describe more fatigue in female cancer patients, it is unclear if this is due to underlying biological factors or reporting biases. The use of preclinical approaches may provide greater insight into this relationship. Therefore, we initiated a series of studies comparing behavioral fatigue measured by decreases in voluntary wheel running in response to cancer therapy in a murine model of head and neck cancer. In mice implanted with leg tumors, combined cisplatin and radiotherapy resulted in a robust reduction in wheel running with no significant differences between male and female mice. In response to cisplatin alone, female mice showed a slower recovery of wheel running after treatment. Finally, in response to cisplatin and immunotherapy with an anti-PD-1 monoclonal antibody, female mice showed a trend toward a greater reduction in wheel running. Overall our data indicates that female sex may be associated with enhanced vulnerability to fatigue following cancer therapy. Our current research explores the possible immunological mechanism underlying this increased vulnerability.