Mediators involved in the cancer anorexia-cachexia syndrome: past, present, and future

The cachectic syndrome, characterized by a marked weight loss, anorexia, asthenia, and anemia is invariably associated with the presence and growth of the tumor and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumor and the host leads to an accelerated starvation state, which promotes severe metabolic disturbances in the host, including hypermetabolism, which leads to an increased energetic inefficiency. Although the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. Present investigation is devoted to revealing the different signaling pathways, in particular transcriptional factors involved in muscle wasting. The main aim of the present review is to summarize and evaluate the different molecular mechanisms and catabolic mediators (both humoral and tumoral) involved in cancer cachexia since they may represent targets for future promising clinical investigations.