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

A Faggiano; V Ramundo; A Dicitore; S Castiglioni; MO Borghi; R Severino; P Ferolla; L Crino; A Abbruzzese; P Sperlongano; M Caraglia; D Ferone; Leo Hofland; A Colao; G (Giovanni) Vitale

doi:10.1111/j.1582-4934.2011.01438.x

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

A Faggiano, V Ramundo, A Dicitore, S Castiglioni, MO Borghi, R Severino, P Ferolla, L Crino, A Abbruzzese, P Sperlongano, M Caraglia, D Ferone, Leo Hofland, A Colao, G (Giovanni) Vitale

Internal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

39 Citations (Scopus)

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 510 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 language	Undefined/Unknown
Pages (from-to)	1563-1572
Number of pages	10
Journal	Journal of Cellular and Molecular Medicine
Volume	16
Issue number	7
DOIs	https://doi.org/10.1111/j.1582-4934.2011.01438.x
Publication status	Published - 2012

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10.1111/j.1582-4934.2011.01438.x

http://hdl.handle.net/1765/68845

Cite this

Faggiano, A., Ramundo, V., Dicitore, A., Castiglioni, S., Borghi, MO., Severino, R., Ferolla, P., Crino, 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

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title = "Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study",

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 510 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.",

author = "A Faggiano and V Ramundo and A Dicitore and S Castiglioni and MO Borghi and R Severino and P Ferolla and L Crino and A Abbruzzese and P Sperlongano and M Caraglia and D Ferone and Leo Hofland and A Colao and Vitale, {G (Giovanni)}",

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Faggiano, A, Ramundo, V, Dicitore, A, Castiglioni, S, Borghi, MO, Severino, R, Ferolla, P, Crino, 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, vol. 16, no. 7, pp. 1563-1572. https://doi.org/10.1111/j.1582-4934.2011.01438.x

TY - JOUR

T1 - Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study

AU - Faggiano, A

AU - Ramundo, V

AU - Dicitore, A

AU - Castiglioni, S

AU - Borghi, MO

AU - Severino, R

AU - Ferolla, P

AU - Crino, L

AU - Abbruzzese, A

AU - Sperlongano, P

AU - Caraglia, M

AU - Ferone, D

AU - Hofland, Leo

AU - Colao, A

AU - Vitale, G (Giovanni)

PY - 2012

Y1 - 2012

N2 - 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 510 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.

AB - 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 510 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.

U2 - 10.1111/j.1582-4934.2011.01438.x

DO - 10.1111/j.1582-4934.2011.01438.x

M3 - Article

C2 - 21883896

SN - 1582-1838

VL - 16

SP - 1563

EP - 1572

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

IS - 7

ER -