Platinum-induced muscle wasting in cancer chemotherapy: Mechanisms and potential targets for therapeutic intervention

Platinum-based drugs are among the most effective anticancer therapies, integrating the standard of care for numerous human malignancies. However, platinum-based chemotherapy induces severe side-effects in cancer patients, such as cachexia. Weight loss, as well as fatigue and systemic inflammation are characteristics of this syndrome that adversely affects the survival and the quality of life of cancer patients. The signalling pathways involved in chemotherapy-induced cachexia are still to be fully understood, but the activity of several mediators associated with muscle wasting, such as myostatin and pro-inflammatory cytokines are increased by platinum-based drugs like cisplatin. Indeed, the molecular mechanisms behind chemotherapy-induced muscle wasting seem to be similar to the ones promoted by cancer in treatment-naive patients. Although some therapeutic agents are under investigation for treating muscle wasting in cancer patients, no effective treatment is yet available. Herein, we review the molecular mechanisms proposed to be involved in chemotherapy-related muscle wasting with a focus on the typical platinum-based drug cisplatin. Therapeutic strategies presently under investigation are also reviewed, providing an overview of the current efforts to preserve muscle mass and quality of life among cancer patients.