Emerging signaling mediators in the anorexia–cachexia syndrome of cancer

Recent findings have revealed new information on the likely roles of activin A and myostatin, and have identified GDF15 and lipocalin-2 as new signaling mediators of the cancer cachexia syndrome. These developments have led to several translational efforts including early-phase clinical trials. Additional data from cancer patients and late-stage clinical trials will be necessary to determine whether activin A, myostatin, GDF15, or lipocalin-2 will ultimately translate to actionable targets to treat cancer cachexia. The future of anti-cachexia treatment may lie in strategies involving more targeted and personalized approaches. The cachexia syndrome in cancer is characterized by weight loss resulting from the combination of anorexia and atrophy of adipose and skeletal muscle. For decades, inflammatory circulatory factors have been identified to regulate wasting, but inhibitors of these factors have not yielded the same clinical benefit as in animal models. Therefore, additional mediators of cachexia likely regulate this syndrome, and such factors might be more suitable for targeted intervention. We highlight several anorexia–cachexia signaling mediators, including activin A, myostatin, GDF15, and lipocalin-2. We discuss current evidence that these factors associate with cachexia in cancer patients, and summarize translational efforts including essential early-phase clinical trials. We conclude with thoughts on targeted and personalized approaches for future anti-cachexia treatments. The cachexia syndrome in cancer is characterized by weight loss resulting from the combination of anorexia and atrophy of adipose and skeletal muscle. For decades, inflammatory circulatory factors have been identified to regulate wasting, but inhibitors of these factors have not yielded the same clinical benefit as in animal models. Therefore, additional mediators of cachexia likely regulate this syndrome, and such factors might be more suitable for targeted intervention. We highlight several anorexia–cachexia signaling mediators, including activin A, myostatin, GDF15, and lipocalin-2. We discuss current evidence that these factors associate with cachexia in cancer patients, and summarize translational efforts including essential early-phase clinical trials. We conclude with thoughts on targeted and personalized approaches for future anti-cachexia treatments.