INS and obesity due to melanocortin 4 receptor deficiency: Insulin and IGF-1 signal through the Akt/PI3K/mTOR cascade to promote cell growth and proliferation, while inhibiting cell survival.33 Notably, the Akt/PI3K/mTOR cascade is also one of the signal mediators of obesity-associated factors, such as leptin, adiponectin, and inflammatory cytokines20 and is the most frequently mutated pathway in human cancers.20,34,35 Accordingly, while certainly not the only pathway of interest, the Akt/PI3K/mTOR cascade has become a focus of the obesity and cancer connection.