NR4A1 and breast carcinoma: It was recently approved by the FDA for hormone receptor-positive, HER2/neu-negative advanced breast cancer, for the treatment of well- or moderately differentiated neuroendocrine tumors of pancreatic origin in adults with progressive disease.37, 38 To date, mTOR inhibitors have shown only modest efficacy in tumors in which they were expected to provide important benefits and patients develop resistance to therapy and progress.39 Resistance to therapy may occur either through intrinsic or extrinsic mechanisms.