Identifying and mechanizing tumor-secreted factors essential to cachexia development is a critical goal of our group. We previously identified that tumor-secreted cytokine leukemia inhibitory factor (LIF) drives appetite suppression and adipose wasting in cancer cachexia. (Arora and Gupta et al., 2017, JCI Insight). LIF is a member of the IL-6 family of cytokines, which trigger surges of inflammation (“cytokine storms”) in acute and chronic disease states. Accordingly, we demonstrated that small-molecule inhibitors of JAK suppress cachexia by LIF and cancer (Arora and Gupta et al., 2018, JCSM Rapid Communications). These studies have led us to a model, in which tumor-secreted inflammatory signals drive anorexia and adipose wasting during cachexia. To this end, we are currently applying parallel in vivo and in vitro approaches to identify the critical signaling mediators of cachexia-mediated anorexia and adipose wasting.