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

A. Faggiano, V. Ramundo, A. Dicitore, S. Castiglioni, M. O. Borghi, R. Severino, P. Ferolla, L. Crinò, A. Abbruzzese, P. Sperlongano, M. Caraglia, D. Ferone, L. Hofland, A. Colao, G. Vitale

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1563-1572
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Keywords

  • Calcitonin
  • Everolimus
  • Medullary thyroid cancer
  • Neuroendocrine tumour
  • Somatostatin analogues

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Faggiano, A., Ramundo, V., Dicitore, A., Castiglioni, S., Borghi, M. O., Severino, R., Ferolla, P., Crinò, L., Abbruzzese, A., Sperlongano, P., Caraglia, M., Ferone, D., Hofland, L., Colao, A., & Vitale, G. (2012). Everolimus is an active agent in medullary thyroid cancer: A clinical and in vitro study. Journal of Cellular and Molecular Medicine, 16(7), 1563-1572. https://doi.org/10.1111/j.1582-4934.2011.01438.x