Intramuscular CMT-167 Tumors Produce a Mild Cachexia Phenotype in C57BL/6J Mice

Area of Science:

• Oncology
• Pathology
• Pharmacology

Background:

• Cancer cachexia is a severe syndrome impacting ~50% of cancer patients, characterized by muscle and fat loss.
• Lung cancer has a high comorbidity with cancer cachexia, necessitating better preclinical models.
• Current models are insufficient for studying the complex relationship between lung cancer and cachexia.

Purpose of the Study:

• To characterize the cachexia phenotype in the CMT-167 syngeneic lung cancer model.
• To evaluate the CMT-167 model's utility for studying cancer cachexia and immune checkpoint inhibitors.
• To establish a novel preclinical model for lung cancer-induced cachexia.

Main Methods:

• Male C57BL6/J mice received intramuscular injections of CMT-167 lung cancer cells or vehicle.
• Cachexia features were assessed 23 days post-injection, including tissue mass, myofiber cross-sectional area (CSA), and circulating biomarkers.
• Pharmacokinetics of pembrolizumab were studied to assess the influence of tumor status on antibody clearance.

Main Results:

• CMT-167 tumor-bearing mice showed reduced adipose and skeletal muscle mass (gastrocnemius, quadriceps) and myofiber CSA compared to tumor-free controls.
• Increased circulating cachexia markers (IL-6, TNF-α) were observed, but without changes in key muscle E3 ubiquitin ligase mRNA.
• Tumor-bearing mice exhibited increased clearance of pembrolizumab, an anti-PD-1 antibody, indicating altered immune checkpoint inhibitor pharmacokinetics.

Conclusions:

• The intramuscular CMT-167 model represents a syngeneic model of mild cancer cachexia.
• This novel mouse model is suitable for investigating cancer cachexia induction, skeletal muscle atrophy, and immune checkpoint inhibitor clearance in lung cancer.
• The CMT-167 model offers a valuable tool for advancing research in oncology and cachexia.