Researchers have uncovered a previously unrecognized pathway linking lung tumor genetics, diet, and the nervous system that drives cancer-associated cachexia, according to a new study in mice. The findings suggest that this newly identified tumor-to-nerve signaling pathway could present a potential therapeutic target for the condition. Cancer-associated cachexia (CAC) is a debilitating syndrome in which cancer patients experience severe, involuntary weight loss and muscle wasting, along with reduced appetite. The condition greatly worsens quality of life, limits patients’ ability to tolerate treatment, and can reduce overall survival. However, there are currently no effective therapies to treat CAC. Although research has identified tumor-derived molecules that promote cachexia, the roles of specific cancer-causing mutations and dietary factors in driving the disease remain poorly understood.

Using genetically modified mouse models, Michael Cross and colleagues examined how common genetic mutations in lung cancer interact with diet to influence cachexia. Cross et al. compared tumors with different genetic alterations, examined the effects of a high-fat, high-calorie diet, analyzed prostaglandin E2 (PGE₂) signaling, and tested genetic, dietary, pharmacological, and nerve-targeting interventions to determine how cachexia develops. They found that mice with lung tumors bearing mutations in the tumor-suppressing gene serine/threonine kinase 11 (Lkb1) developed CAC. Notably, feeding these mice a high-fat diet to rescue cachexia instead made the condition substantially worse by sharply reducing their food and water intake as well as physical activity. The diet also accelerated mortality, even without increasing tumor burden. Cross et al. discovered that the inflammatory molecule prostaglandin E2 (PGE2) was a key driver of this effect. According to the findings, Lkb1-mutant tumors produced elevated levels of PGE2, and a high-fat diet further increased its production. Blocking PGE2 synthesis, either genetically or with drugs, restored appetite and improved survival. Moreover, the authors found that disrupting lung sensory nerve signaling prevented PGE2-dependent cachexia, indicating that local tumor signals transmitted through sensory nerves to the brain can contribute to CAC. “Cachexia probably reflects a spectrum of mechanistically distinct but phenotypically convergent states rather than emerging from a single cause,” write Yetiş Gültekin and Matthew Vander Heiden in a related Perspective. ”Nevertheless, defining how tumors recruit neural circuits to sustain their own metabolism and to reshape host physiology will be important to understand both cancer and cachexia biology.“

Human embryo models are laboratory-grown models derived from human stem cells that mimic aspects of early human development. They are increasingly used to study developmental processes and infertility, raising new questions about how this research should be regulated. In April 2026, Japan introduced revised guidelines covering human embryo model research. Under the new framework, all such research now requires ethics review and notification to the national government.

To understand how these changes fit within the broader international landscape, Professor Misao Fujita, Assistant Professor Kyoko Akatsuka, and Researcher Fujika Ariarakawa of the Institute for the Advanced Study of Human Biology (WPI-ASHBi) and the Center for iPS Cell Research and Application (CiRA), Kyoto University, compared the Japanese guidelines with the 2025 guidelines of the International Society for Stem Cell Research (ISSCR). While the two guidelines are broadly consistent, important differences remain in how some areas of research are defined and regulated. The study highlights the need for researchers, ethics review committees, regulatory authorities, academic societies, and journals to work closely together as the field continues to evolve.

These findings were published in Cell Stem Cell on 2 July 2026.