Alleviating side effects

Abstract

Cancer Platinum-based chemotherapy drugs, such as cisplatin and oxaliplatin, are commonly used to treat diverse cancer types. However, their use is limited by side effects, particularly vomiting, anorexia, muscle wasting, and weight loss. Breen et al. show that the amounts of the cytokine growth differentiation factor 15 (GDF15) increase in the circulation of patients with colorectal cancer, non–small cell lung cancer (NSCLC), and ovarian cancer who were treated with platinum chemotherapy. Moreover, the amount of circulating GDF15 was correlated with weight loss in metastatic colorectal cancer patients receiving oxaliplatin. Neutralization of GDF15 using monoclonal antibodies in nonhuman primates treated with cisplatin attenuated vomiting and anorexia. GDF15 also reversed weight loss in mice with NSCLC treated with cisplatin. This work shows that GDF15 has a causal role in these side effects and could be targeted to enable optimal chemotherapy treatment. Cell Metab. 32 , 938 (2020).