Abstract Cancer cachexia is a systemic wasting condition that affects multiple organs and failure to recover from the condition ultimately leads to death. It is estimated to affect as many as 80% of patients with cancer and accounts for up to 20% of cancer deaths. Cancer cachexia is characterized by negative energy balance leading to weight loss and organ atrophy. Cancer cachexia results in decreased physical ability, reduced therapy efficacy, and increased mortality and morbidity. There is emerging evidence that hormone signaling drives inter-organ changes in cancer cachexia development, including changes in the brain, liver and muscle. I have developed a cancer cachexia mouse model in which both cancer cachexia development and recovery can be studied in the same animal. Using this model, I observed decreased muscle mass during cancer cachexia development and increased muscle mass during cancer cachexia recovery. By performing unbiased analyses on quadriceps RNA sequencing data from cachectic and recovering mouse, I identified a cluster of genes indicating alterations in the neuromuscular junctions. This suggests that neuromuscular junctions (NMJ) may play a role in muscle atrophy and regeneration in cancer cachexia. By focusing my analyses on circulating hormones, I identified apelin as the most upregulated hormone in the skeletal muscle during cancer cachexia recovery. Apelin has been associated with age-related muscle atrophy, muscle function and the neuromuscular junction. I have modulated apelin level systemically and demonstrated that systemic apelin administration decreased intramuscular E3 ligase (protein degradation) and increased Pax7 (regeneration) marker in the lower leg muscle. These findings have been corroborated by detailed histopathology analyses. My work establishes a novel mouse model that enables studying cachexia development and recovery in the same mice. This model may lead to the discovery of new treatment options that can prevent or treat cancer cachexia. In addition, my work suggests that there may be potential targetable mechanisms for accelerating muscle recovery from cancer cachexia. Citation Format: Alice Wang, Tobias Janowitz. Apelin is a candidate driver for neuromuscular junction recovery from cancer cachexia abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4789.
Wang et al. (2026) studied this question.