Skeletal muscle vasculature in cancer-induced cachexia (MyoVasC

• Applicant: Luis Gand
• Subject Area: Anatomy and Physiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581856652

Cancer-induced cachexia (CIC) is a severe whole-body syndrome affecting up to 80 % of cancer patients while significantly contributing to mortality. It is defined as the involuntary loss of muscle and/or fat mass, resulting in ≥ 5 % loss of body mass over 6 months. Until today, no pharmacological intervention is approved for the treatment of CIC, except for Anamorelin in Japan. Therefore, understanding the underlying mechanisms resulting in uncontrolled muscle mass loss is of utmost priority. The molecular mechanisms underlying skeletal muscle wasting in CIC have been studied over the last decades, yet no pharmacological intervention has successfully ameliorated cachectic wasting. This hints to our still poor understanding of the underlying mechanisms. Muscle vasculature is vital for muscle homeostasis by supplying nutrients and oxygen and clearing metabolic waste products. The MyoVasC study aims to investigated skeletal muscle and its vascular network in cachectic conditions. I hypothesize, that muscle vasculature is strongly perturbed by the underlying cachectic condition, resulting in diminished supply with oxygen and nutrients. As a model organism I will employ the APCMin/+ mouse that spontaneously develops adenocarcinomas and cachexia. To improve muscle vascularization in cachectic animals I will employ a wheel running exercise intervention. Pro-angiogenic gene therapy using AAV-vectors containing SPARC or VEBF-B will also be studied to improve muscle vasculature. Methodologically, I will employ spatial transcriptomics to unveil transcriptional changes on a subcellular level in a spatial dimension. 3D whole muscle vascular imaging will provide insights into changes in the vascular network. Key findings will be investigated in muscle biopsies from gastrointestinal cancer patients.

• DFG Programme: WBP Fellowship
• International Connection: Finland
• Host: Professorin Riikka Kivelä, Ph.D.