Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study

Journal of Cellular and Molecular Medicine

A. Faggiano⁴  V. Ramundo²  A. Dicitore⁸  S. Castiglioni⁸  M. O. Borghi⁸  R. Severino²  P. Ferolla⁵  L. Crinò⁵  A. Abbruzzese⁶  P. Sperlongano¹  M. Caraglia⁶  D. Ferone⁷  L. Hofland³  A. Colao² 

[1] Department of Surgery, Anesthesiology, and Emergency, Second University of Naples, Naples, Italy;Department of Molecular and Clinical Endocrinology and Oncology, “Federico II” University of Naples, Naples, Italy;Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands;IRCCS Fondazione SDN, Naples, Italy;Multidisciplinary Group for Diagnosis and Therapy of Neuroendocrine Tumours, Umbria Region Cancer Network, Italy;Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy;Department of Endocrinology and Medical Sciences & Center of Excellence for Biomedical Research, University of Genoa, Liguria, Italy;Istituto Auxologico Italiano IRCCS, Milan, Italy

关键词: medullary thyroid cancer;    neuroendocrine tumour;    calcitonin;    somatostatin analogues;    everolimus;   

DOI  :  10.1111/j.1582-4934.2011.01438.x

来源: Wiley

【 摘 要 】

Abstract

Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour effects in different types of neuroendocrine tumours, has never been evaluated in patients with medullary thyroid cancer (MTC). The aim of this study was to evaluate the in vitro and in vivo effects of everolimus in combination with octreotide in MTC. Two patients with progressive metastatic MTC and high calcitonin levels were treated with everolimus 5–10 mg/day. Both patients were under treatment with octreotide LAR at the study entry. An in vitro study was also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1 cells). A tumour response was observed in both patients. Serum calcitonin decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells, everolimus induced a significant dose-dependent inhibition in cell proliferation. This effect seems to be related to a cell cycle arrest in G₀/G₁ phase in both cell lines and to the induction of cellular senescence in TT cells. Everolimus in combination with octreotide may be active as anti-tumour therapy in patients with progressive metastatic MTC, suggesting to further evaluate this agent in MTC patients in a large prospective study.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd