STAT3 and cancer: The constitutive activation of STAT3 in cancer cells represents a biochemical aberrancy, and there are at least four mechanisms shown to contribute to this abnormality: (1) loss of the negative regulation of STAT3; (2) excessive stimulation of STAT3; (3) positive feedback loops that sustain persistent STAT3 activation; (4) somatic mutations that confer a hyperactive property to STAT3.