www.landesbioscience.com JAK-STAT 261

So-called oncogenic transcription factors are not themselves mutated in cancer, but mediate the effects of a diverse array of activated kinases in regulating the genes that control prolif-eration, survival, invasion and spread that underlie malignancy. Reflecting their role in the physiological control of these pro-cesses, STAT family members, particularly STAT3 and STAT5, were found to be activated inappropriately in a wide range of human cancers. Inhibition of these proteins in cancer models shows significant therapeutic benefit; by contrast, loss of func-tion in normal cells is well tolerated, likely due to redundancies in physiological signal transduction. Thus, STATs appear to be targets with the potential for a high therapeutic index. However, while great progress has been made in developing inhibitors to a range of kinases, the ability to target transcription factors has lagged far behind. In fact, for a variety of reasons transcriptio