Promising models for cancer-induced cachexia drug discovery

Introduction: Cachexia is a frequent, multifactorial syndrome associated with cancer afflicting patients' quality of life, their ability to tolerate anti-neoplastic therapies and the therapies efficacy, as well as survival. Currently, there are no approved cancer cachexia treatments other than those for the treatment of the underlying cancer. Cancer cachexia (CC) is poorly understood and hence makes clinical trial design difficult at best. This underlines the importance of well-characterized animal models to further elucidate the pathophysiology of CC and drug discovery/development. Areas covered: This review gives an overview of the available animal models and their value and limitations in translational studies. Expert opinion: Using more than one CC model to test research questions or novel compounds/treatment strategies is strongly advisable. The main reason is that models have unique signaling modalities driving cachexia that may only relate to subgroups of cancer patients. Human xenograph CC models require the use of mice with a compromised immune system, limiting their value for translational experiments. It may prove beneficial to include standard care chemotherapy in the experimental design, as many chemotherapeutic agents can induce cachexia themselves and alter the metabolic and signaling derangements of CC and thus the response to new therapeutic strategies.