The cancer anorexia-cachexia syndrome (CACS) is primarily characterized by anorexia, weight loss, and muscle wasting. CACS causes a decline of the clinical status of cancer patients and often becomes a life-threatening condition, increasing mortality, reducing treatment success and producing severe psychological suffering of patients. Despite its clinical relevance, no pharmacological treatment is approved for its therapy.

Type 2 Diabetes Mellitus (T2DM) and cancer progression have similar metabolic alterations that affect regulation in energetic pathways including Insulin resistance and reduced glucose tolerance. Interestingly, pre-clinical data from tumor-bearing rodents demonstrated some beneficial effects of glucagon-like peptide 1 receptor (GLP-1R) analogs. However, their strong hypoghagic effects represent a limitation, especially for patients that suffer from co-morbidities associated with a pre-existing state of anorexia and cachexia.

Glucose-dependent insulinotropic polypeptide (GIP), known for its function as an incretin hormone controlling blood glucose levels, may provide a better therapeutic strategy. While GIP-based therapeutics were cast aside due to its overall weak hypophagic effects compared to GLP-1 analogs in the context of obesity and diabetes, recent studies employing long acting second-generation GIP-analogs showed promising results in terms of glucose handling with minimal effects on feeding, and with even potential antiemetic effects.

This summer, I was given the opportunity to work in Dr. Bart De Jonghe’s Laboratory under the supervision of Dr. Tito Borner. Using hepatoma tumor-bearing (TB) rats, a well characterized pre-clinical model for CACS, insulin and glucose levels at regular intervals following tumor-induction in rats were measured, and the effects of a long-acting GIP on feeding and on glucose intolerance were subsequently studied in both healthy and tumor-bearing rats.

Long-acting GIP retains its blood lowering properties upon chronic administration without any effects on feeding nor body weight in healthy rats. Furthermore, ongoing experiments suggest the presence of impaired glucose homeostasis that precedes the onset of an anorectic response. Current studies are evaluating the beneficial effect of long-acting GIP chronic treatment in tumor-bearing rats.

Future lines of research will include the assessments of malaise to understand whether GIP can also prevent malaise induced by tumor growth. Furthermore, the ability of GIP-based treatments to also prevent muscle loss following tumor growth will also be investigated. Altogether, these efforts can narrow the gap in the literature on the role of GIP in the regulation of energy homeostasis and provide new therapeutic venues.

During this project, I worked with animal models, learned how to accurately measure feeding behavior, glucose, and insulin levels; and gained the principles of cell culture and aseptic techniques. I am extremely grateful for the mentorship that I received as well as the opportunity to contribute to this field of nausea and emesis.