Pituitary

, Volume 15, Issue 1, pp 37–43

New targeted therapies in pituitary carcinoma resistant to temozolomide

Authors

  • Emmanuel Jouanneau
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
  • Anne Wierinckx
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Université de Lyon, Lyon1
    • Inserm U1052Centre de Recherche en Cancérologie de Lyon
  • François Ducray
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
  • Véronique Favrel
    • Service de radiothérapieCentre Hospitalier Universitaire Lyon Sud
  • Françoise Borson-Chazot
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
  • Jérôme Honnorat
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
  • Jacqueline Trouillas
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
    • INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research CenterNeuro-Oncology and Neuro-inflammation Team
    • Fédération d’Endocrinologie (GR, FBC), Service de Neurologie (FD, JH), Service de Neurochirurgie (EJ), Centre de Pathologie Est (JT), Groupement Hospitalier EstHospices Civils de Lyon
    • Université de Lyon, Lyon1
    • Fédération d’Endocrinologie du Pole EstHospices Civils de Lyon
Article

DOI: 10.1007/s11102-011-0341-0

Cite this article as:
Jouanneau, E., Wierinckx, A., Ducray, F. et al. Pituitary (2012) 15: 37. doi:10.1007/s11102-011-0341-0

Abstract

To evaluate the antitumoral efficacy of everolimus in pituitary carcinoma resistant to temozolomide, the correlation with mammalian target of rapamycin (mTOR) signaling in the tumor and to present recent advances and future treatments of pituitary carcinomas. Pituitary carcinomas are rare and largely unresponsive to current treatment options. Recent reports on the antitumoral efficacy of temozolomide in some such patients are encouraging, yet most patients appear to show resistance to its actions. As a potential alternative, the mTOR inhibitor, everolimus, has been shown to potently inhibit pituitary cell proliferation highlighting mTOR inhibition as a promising therapeutic approach for pituitary carcinomas. We described the tumoral effects of a combination therapy with everolimus (5 mg/day) and octreotide (30 mg/month) and the mTOR signalling expression in a patient with pituitary ACTH carcinoma, compared to 17 other ACTH adenomas. Clinical and biochemical evaluation were performed every month, and imaging after 3 month of treatment. mTOR signaling was assessed by microarray expression analysis of each of the 18 adenoma tissues. Combined therapy failed to control pituitary tumor growth and ACTH secretion. Slight activation of mTOR signaling was found in all ACTH tumors alongside important variations between tumors. Low antitumor efficacy shown by everolimus might be explained by the weak activation of mTOR pathway in ACTH tumors. Everolimus treatment was inefficient at controlling secretion and tumor growth of one ACTH pituitary carcinoma. More clinical cases, with mTOR signalling expression analysis of the tumor, must be published before any conclusions can be drawn.

Keywords

Pituitary carcinomamTOREverolimusTemozolomidePituitary adenomaSilent ACTH tumor

Copyright information

© Springer Science+Business Media, LLC 2011