Cancer Cachexia and the Brain Stem

This editorial examines the role of the brain stem in cancer cachexia, focusing on growth differentiation factor 15 (GDF 15), a cytokine implicated in anorexia and nausea. A phase 2 trial of ponsegromab (a GDF 15 neutralizing monoclonal antibody) demonstrated efficacy in patients with lung, pancreatic, or colorectal cancers, showing median weight gain of 2.81 kg and improved muscle mass over 12 weeks. The brain stem’s area postrema and nucleus tractus solitarius mediate GDF 15’s anorexigenic effects, linking tumor derived and chemotherapy induced GDF 15 to cachexia. While promising, questions remain about long term durability, optimal dosing, and concurrent pathways (e.g., interleukin 6). The article highlights the need to integrate neuroscience insights from obesity research to develop targeted therapies for cachexia’s multifactorial mechanisms.

This editorial examines the role of the brain stem in cancer cachexia, focusing on growth differentiation factor 15 (GDF 15), a cytokine implicated in anorexia and nausea. A phase 2 trial of ponsegromab (a GDF 15 neutralizing monoclonal antibody) demonstrated efficacy in patients with lung, pancreatic, or colorectal cancers, showing median weight gain of 2.81 kg and improved muscle mass over 12 weeks. The brain stem’s area postrema and nucleus tractus solitarius mediate GDF 15’s anorexigenic effects, linking tumor derived and chemotherapy induced GDF 15 to cachexia. While promising, questions remain about long term durability, optimal dosing, and concurrent pathways (e.g., interleukin 6). The article highlights the need to integrate neuroscience insights from obesity research to develop targeted therapies for cachexia’s multifactorial mechanisms.