Pathogenesis of cancer cachexia Cancer cachexia, a complex syndrome that occurs in most of cancer patients, is characterized by body weight loss and marked skeletal muscle wasting. Cachexia negatively impacts on patient management, tolerance to antineoplastic treatments and quality of life. Recent data suggest that impaired myogenesis and tissue protein hypercatabolism contribute to the pathogenesis of cachexia. In addition, tumor-derived extracellular vesicles (EV) also seem to play a role. The study is aimed to investigate the pathogenesis of cancer-induced muscle wasting by taking advantage of both in vivo and in vitro model systems, focusing on the following aspects: 1) mitochondrial biogenesis, dynamics, number and function; 2) effects of exercise and/or exercise mimetic drugs in modulating muscle wasting in tumor-bearing animals; 3) muscle-specific microRNAs as mediators and biomarkers of cachexia; 4) role of EVs in mediating the metabolic derangements that characterize cancer cachexia. Autophagy in cell death and survival Autophagy is the major intracellular catabolic pathway essential to living cells and represents the most effective mechanism for removal of damaged or unnecessary molecules/organelles. The role of autophagy, however, is not limited to substrate degradation; indeed, it was also suggested to participate to cell death. Autophagy is now recognized as a protective mechanism promoting cell survival in adverse or stress conditions, including hypoxia and redox imbalance. The research project will mostly focus on liver and breast cancer-derived cell lines and will be aimed at: 1) understanding whether upregulated autophagy plays a key role in the resistance of neoplastic cells to anticancer drugs, 2) identifying the molecular mechanism(s) by which this occurs and 3) evaluating whether selectively targeting autophagy may represent a suitable strategy to overcome resistance of tumor cells to anticancer drugs.