Understanding sex differences in the regulation of cancer-induced muscle wasting

Abstract

Purpose of review: We highlight evidence for sexual dimorphism in preclinical and clinical studies investigating the cause and treatment of cancer cachexia.

Recent findings: Cancer cachexia is unintended bodyweight loss occurring with cancer, and skeletal muscle wasting is a critical predictor of negative outcomes in the cancer patient. Skeletal muscle exhibits sexual dimorphism in fiber type, function, and regeneration capacity. Sex differences have been implicated in skeletal muscle metabolism, mitochondrial function, immune response to injury, and myogenic stem cell regulation. All of these processes have the potential to be involved in cancer-induced muscle wasting. Unfortunately, the vast majority of published studies examining cancer cachexia in preclinical models or cancer patients either have not accounted for sex in their design or have exclusively studied males. Preclinical studies have established that ovarian function and estradiol can affect skeletal muscle function, metabolism and mass; ovarian function has also been implicated in the sensitivity of circulating inflammatory cytokines and the progression of cachexia.

Summary: Females and males have unique characteristics that effect skeletal muscle's microenvironment and intrinsic signaling. These differences provide a strong rationale for distinct causes for cancer cachexia development and treatment in males and females.

Figure 1:

Potential Targets of Estrogen in Muscle in the Systemic Cachectic Environment

Figure 2:

Cancer Environment’s Effect on Dysregulated Protein Turnover in Skeletal Muscle