REVIEW  ACROMEGALY TODAY FOR CLINICAL PRACTICE 

Minerva Endocrinologica 2019 June;44(2):109-28

DOI: 10.23736/S0391-1977.19.02970-5

Copyright © 2019 EDIZIONI MINERVA MEDICA

language: English

Molecular determinants of the response to medical treatment of growth hormone secreting pituitary neuroendocrine tumors

Antonio C. FUENTES-FAYOS ^{1, 2, 3, 4}, Araceli GARCÍA-MARTÍNEZ ⁵, Aura D. HERRERA-MARTÍNEZ ^{1, 2, 3, 4}, Juan M. JIMÉNEZ-VACAS ^{1, 2, 3, 4}, Mari C. VÁZQUEZ-BORREGO ^{1, 2, 3, 4}, Justo P. CASTAÑO ^{1, 2, 3, 4}, Antonio PICÓ ⁶, Manuel D. GAHETE ^{1, 2, 3, 4}, Raúl M. LUQUE ^{1, 2, 3, 4} ✉

¹ Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain; ² Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain; ³ Reina Sofia University Hospital (HURS), Cordoba, Spain; ⁴ CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain; ⁵ Research Laboratory, Hospital General Universitario de Alicante-Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; ⁶ Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante-ISABIAL, Miguel Hernández University, CIBERER, Alicante, Spain

Acromegaly is a chronic systemic disease mainly caused by a growth hormone (GH)-secreting pituitary neuroendocrine tumor (PitNETs), which is associated with many health complications and increased mortality when not adequately treated. Transsphenoidal surgery is considered the treatment of choice in GH-secreting PitNETs, but patients in whom surgery cannot be considered or with persistent disease after surgery require medical therapy. Treatment with available synthetic somatostatin analogues (SSAs) is considered the mainstay in the medical management of acromegaly which exert their beneficial effects through the binding to a family of G-protein coupled receptors encoded by 5 genes (SSTR1-5). However, although it has been demonstrated that the SST1-5 receptors are physically present in tumor cells, SSAs are in many cases ineffective (i.e. approximately 10-30% of patients with GH-secreting PitNET are unresponsive to SSAs), suggesting that other cellular/molecular determinants could be essential for the response to the pharmacological treatment in patients with GH-secreting PitNETs. Therefore, the scrutiny of these determinants might be used for the identification of subgroups of patients in whom an appropriate pharmacological treatment can be successfully employed (responders vs. non-responders). In this review, we will describe some of the existing, classical and novel, genetic and molecular determinants involved in the response of patients with GH-secreting PitNETs to the available therapeutic treatments, as well as new molecular/therapeutic approaches that could be potentially useful for the treatment of GH-secreting PitNETs.

KEY WORDS: Pituitary neoplasms - Neuroendocrine tumors - Acromegaly - Growth hormone-secreting pituitary adenoma