Abstract 679: Serine/threonine kinase inhibitors on improving symptoms of neuroendocrine tumor

Abstract

Recently, neuroendocrine tumors (NETs) are increased and mostly occurred in gastrointestinal tract and lung in the worldwide. It secretes functional hormones and non-functional neural transmitters to affect patients unwell so called carcinoid syndrome. In clinically, surgical removal and somatostatin treatment are used to ease the syndrome by NETs. A new strategy for advanced NETs is used by targeting mTOR signaling and neovascularization. In 2011, Everolimus, an mTOR inhibitor, was approved for the treatment of progressive NETs of pancreatic origin in patients with unresectable, locally advanced or metastatic disease, but safety and effectiveness of everolimus have not been established. In this study, low dose of mTOR inhibitor was investigated for capability in modifying the carcinoid syndrome. In an NCI-H727 NET xenograft model, the level of chromogranin A (CgA) was determined in accordance with tumor volume. With multiplexing the serum hormones, alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin were lowered in tumor-bearing mice, but they were rebound when animals treated with Everolimus. Another mTOR inhibitor INK 128 had no apparent tumor inhibition in the same model with doses ranged from 0.25-1 mg/kg. There was no change in the level of CgA in INK128-treated tumor-bearing mice but alpha-MSH level was restored compared with normal mice at a dose-dependent manner. In conclusion, we discovered that low dose of mTOR inhibitor could modify the carcinoid syndrome, where alpha-MSH and beta-endorphin may serve as biomarkers for prognoses of mTOR treatment. Citation Format: I-Hua Liu, Yusian Ding, Chiung-Wen Liou, Jia-Ming Chang. Serine/threonine kinase inhibitors on improving symptoms of neuroendocrine tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 679. doi:10.1158/1538-7445.AM2017-679