Snoke, Deena B., van der Velden, Jos L.J.L., Bellafleur, Emma R., Dearborn, Jacob S., Lenahan, Sean M., Beal, Alexandra E., Aboushousha, Reem, Heininger, Skyler C.J., Ather, Jennifer L., & Mank, Madeleine M. (2025). Early adipose tissue wasting in a preclinical model of human lung cancer cachexia. Cell Reports, 44(9), 116278. https://doi.org/10.1016/j.celrep.2025.116278
This study focuses on cancer cachexia (CC), a condition where patients lose skeletal muscle and fat, which makes them less responsive to treatments and increases the risk of death. There are currently no approved treatments for CC, partly because animal models often do not accurately reflect human disease. To create a more relevant model for lung cancer–related CC, researchers developed mice with a specific genetic mutation in lung epithelial cells (KrasG12D/+, called G12D mice). These mice gradually develop CC and show tissue, cellular, genetic, and metabolic changes similar to those seen in humans with lung CC. One early sign in these mice is fat loss, a feature also observed in many CC models and in lung cancer patients. The study found that factors released by tumors trigger fat breakdown, which drives the loss of adipose tissue, and that this fat loss is not directly proportional to tumor size. Overall, G12D mice replicate important aspects of human lung CC and reveal that early tumor-driven changes in fat metabolism play a key role in the development of cachexia.
Figure 1
Characterization of lung epithelial cell-specific, inducible KrasG12D/+ (G12D) mice at 12 weeks post-induction