• Alexandra Moreira-Pais CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal; LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal; Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal
  • Rita Ferreira LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
  • Vera Marisa Costa UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
  • Paula A. Oliveira Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal
  • José A. Duarte CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal; TOXRUN – Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, Gandra, Portugal


Chemotherapeutic agents like doxorubicin (DOX) are the foundation for the treatment of a variety of malignancies; however, these therapies have several side-effects. DOX may trigger or potentiate the muscle wasting observed in cancer patients, which is particularly worrying in frail old patients. Therefore, it is important to comprehend the mechanisms responsible for DOX-induced toxicity in skeletal muscle, to identify therapeutic targets envisioning the improvement of survival rates and quality of life of these patients. Hence, this review discusses the molecular players that may be involved in DOX-induced muscle wasting. From the analysis performed herein, DOX seems to induce the activation of the proteolytic ubiquitin proteasome pathway (UPP), which in turn can also be enhanced by DOX-induced increase in myostatin and tumor necrosis factor (TNF)-α signaling pathways, as well as insulin resistance. Furthermore, DOX-induced oxidative stress and mitochondrial dysfunction may also be critical contributors for muscle wasting. All these mechanisms may contribute to the loss of skeletal muscle mass and function observed after DOX exposure, which may lead to or aggravate cachexia, responsible for more than 20% of all cancer-related deaths.


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Author Biography

José A. Duarte, CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal; TOXRUN – Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, Gandra, Portugal



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How to Cite
MOREIRA-PAIS, Alexandra et al. THE MOLECULAR MECHANISMS INVOLVED IN DOXORUBICIN-INDUCED SKELETAL MUSCLE WASTING. Revista Portuguesa de Cirurgia, [S.l.], n. 51, p. 13-22, feb. 2022. ISSN 2183-1165. Available at: <>. Date accessed: 03 oct. 2023. doi:
Original Papers