IGF2 and adrenal cortex carcinoma: Evidence also suggests that the IGF-1R plays a pivotal role in ACC pathophysiology representing an important therapeutic target in advanced ACC.[43, 45] Indeed, the IGF2 gene and protein expression has been associated with aggressive clinic-pathological features of ACC when assessed by immunohistochemistry and gene expression arrays (i.e., high grade and metastatic disease).[44, 46] These results provided the rationale and fostered the clinical development of anti-IGF antibodies for treatment of this disease.