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

Current Opinion in Endocrinology, Diabetes and Obesity - Tập 24 Số 4 - Trang 301-305 - 2017
Anat Ben-Shlomo1, Odelia Cooper1,2,3
1Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
2e-mail: [email protected]
3to Odelia Cooper, MD, Pituitary Center, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., A6600, Los Angeles, CA 90048, USA. Tel: +1 310 423 2830

Tóm tắt

Purpose of review 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. Recent findings 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. Summary Preclinical and clinical models substantiate the role of the EGFR pathway in corticotroph and lactotroph adenomas. Although further study is needed, results to date suggest that targeting the ErbB pathway may be an effective therapeutic approach for patients with aggressive pituitary tumours.

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Current Opinion in Endocrinology, Diabetes and Obesity

Tập 24 Số 4

301-305

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