Furthermore, the high levels of IL-6, secreted by ES-stroma crosstalk in ES tumor microenvironment, activated the JAK/STAT3 signaling and inducing resistance to the IGF-1R blockade; however, the combination of IGF-1R and STAT3 inhibitors significantly increased sensitivity against the resistance to IGF-1R (Lee et al., 2015; Santoro et al., 2017). Here, IGF1R is linked to neoplasm.