GDF15 in cancer cachexia
Plasma levels of growth differentiation factor 15 (GDF15) are elevated in response to physiological, pharmacological, and pathological stimuli.
GDF15 signals through GDNF family receptor α-like (GFRAL) receptors to control food intake, systemic lipid metabolism, and insulin sensitivity.
GDF15 promotes immunosuppression and plays a protective role in sepsis. Malignant tumors hijack this mechanism to create a microenvironment that protects against immune attack and generates resistance to immunotherapy. GDF15 produced by the fetal placenta plays a protective role during pregnancy.
However, GDF15 levels above a certain threshold cause hyperemesis gravidarum. Maternal sensitivity to GDF15 is determined by its circulating levels before pregnancy.
In early clinical trials, antibodies blocking GDF15 have shown promising results in overcoming resistance to immunotherapy and in reversing aspects of cancer cachexia.
https://www.cell.com/trends/cancer/fulltext/S2405-8033(25)00150-5
