Diversity in chemotherapy-induced cachexia

Preclinical and clinical studies suggest that chronic administration of cytotoxic drugs (e.g., chemotherapy) may contribute to the occurrence of skeletal muscle wasting and weakness/fatigue (i.e., cachexia). Doxorubicin, folfiri, and cisplatin are known to promote cachexia by triggering common alterations such as skeletal muscle atrophy, protein breakdown, and mitochondrial dysfunction, whereas each also possesses distinguishing features in terms of the activated molecular pathways. Similarly, commonalities exist between different cancer types including the development of muscle wasting early in treatment that can persist for years. The impact of treatment for gastrointestinal, head and neck, and nonsmall cell lung cancers (NSCLCs) on the development of cachexia and survival outcomes is well documented. However, a disconnect occurs between preclinical studies on cachexia, which are often performed on younger mice, and clinical studies on cachexia, which are focused on patients over 60 yr old. Yet, several preclinical studies have examined the impact of age on chemotherapy-induced cachexia. Finally, sex differences have been identified in both preclinical and clinical studies focused on the onset of cachexia consequential to chemotherapy administration and raise the question of whether treatments for this condition should be based on sex specificities. In conclusion, although cancer cachexia has been widely studied for its impact on patients affected by various malignancies, the effects of chemotherapy on the development of cachexia are less explored. Here, we examine diversity in chemotherapy-induced cachexia with respect to specific types of chemotherapy regimens and cancer, and differences based on age and sex.