Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside

Current Opinion in Endocrinology, Diabetes, and Obesity
Anat Ben-Shlomo, Odelia Cooper

Abstract

Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease. Using EGFR or human epidermal growth factor receptor 2-driven prolactin (PRL) promoters, transgenic mice develop large tumours that respond to TKI inhibition. In human corticotroph primary cultures, treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib suppresses proopiomelanocortin mRNA. USP8 mutations, detected in up to two-thirds of Cushing disease, may underlie the increase in EGFR signalling in these tumours. Human prolactinomas have differential ErbB receptor expression associated with aggressive behaviour and data from an ongoing clinical trial suggest that resistant prolactinomas may respond to the EGFR TKI lapatinib. Preclinical and clinical models substantiate the ro...Continue Reading

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Citations

Jan 19, 2018·Pituitary·Anat Ben-Shlomo, Odelia Cooper
Nov 7, 2017·International Journal of Molecular Sciences·María José García-BarradoJosé Carretero
Jul 27, 2018·Expert Opinion on Pharmacotherapy·Sylvère Störmann, Jochen Schopohl
Jul 28, 2019·Journal of Clinical Medicine·Mirela Diana IlieGérald Raverot
Nov 14, 2019·Hormones : International Journal of Endocrinology and Metabolism·George Kontogeorgos, Eleni Thodou
Jun 9, 2018·Frontiers in Endocrinology·Mariana FuertesEduardo Arzt
May 18, 2019·Drugs·José Miguel Hinojosa-AmayaMaria Fleseriu
Aug 20, 2020·Expert Review of Endocrinology & Metabolism·Cristina CapatinaMaria Fleseriu
Jun 28, 2019·European Endocrinology·Elena V VarlamovMaria Fleseriu
Oct 8, 2020·International Journal of Molecular Sciences·Ozal BeylerliGjumrakch Aliev
Sep 16, 2020·The Journal of Clinical Endocrinology and Metabolism·Andrew L LinEliza B Geer
Nov 6, 2020·The Journal of Clinical Endocrinology and Metabolism·Odelia CooperShlomo Melmed
May 15, 2021·Frontiers in Endocrinology·José Miguel Hinojosa-AmayaDaniel Cuevas-Ramos
Jul 21, 2021·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Ramazan SariIlhan Elmaci
Sep 9, 2021·Nature Reviews. Endocrinology·Gérald RaverotThierry Brue

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