New Horizons with Growth Differentiation Factor 15 in Oncology: From Cancer Cachexia and Tumour Immunity to Novel Therapeutic Strategies

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine produced by tumour cells and peripheral cells. It is implicated in the development of cancer cachexia, a debilitating condition for which no effective pharmacological therapy currently exists. GDF-15 regulates appetite and metabolic processes through complex neural and hormonal networks. Furthermore, it has been implicated in chemotherapy-induced nausea and vomiting, representing a potential therapeutic target. GDF-15 negatively affects tumour immunity, suggesting that anti-GDF-15 therapy could potentially enhance immune responses and help overcome resistance to immunotherapy. Recently, early clinical trials have reported preliminary results of GDF-15-targeted therapies in alleviating cancer cachexia and potentially enhancing the efficacy of immunotherapy. This review aims to provide an overview of the role of GDF-15 in cancer cachexia, including the underlying neural mechanisms and their involvement in tumour immunity. This review also summarises recent clinical trial findings and discusses future perspectives on GDF-15-targeted therapy in oncology, offering important insights for future research.