In addition to the upstream factors, including cytokine (IL-6) and growth factor receptors (FGFR1/2/3/4 and MET), loss-of-function mutation or treatment-induced loss of “negative regulators”, such as SOCS, SHP-1, PIAS, and PTPRT, which have been reported in various cancer types38–40, may also contribute to aberrant STAT3 activation. This evidence concerns the gene CISH and cancer.