Anabolic resistance in cancer cachexia: a role for sex and chemotherapy

The purpose of this review is to highlight recently published research that can provide insight into how either sex or chemotherapeutics can impact cancer regulation of muscle anabolic resistance. Critical knowledge gaps are emphasized that are linked to cancer and treatment disruptions to muscle anabolic signaling. We speculate and propose a rationale for estrogen's protective effect against cancer-induced muscle anabolic resistance in females. Furthermore, there is growing evidence that many cancer treatments have the potential to exacerbate muscle anabolic resistance in both males and females. We present current evidence and speculate on how nutritional interventions could serve as key modulators of cancer-induced anabolic resistance in these conditions.

Recently published studies have reinforced that sex impacts the regulation of cancer cachexia in several established preclinical models, with males often developing more severe cachexia when compared to females. Importantly, recent research has established these sex differences at the transcriptomic level. Recent research has also strengthened the link between hypogonadism as a driver of cancer cachexia in preclinical models. Furthermore, chemotherapy has the potential to exacerbate muscle anabolic resistance.

There is a growing body of literature that provides a strong rationale for further investigation into the impact of sex and chemotherapy on the cancer regulation of muscle anabolic resistance.