Gadelha Monica R, Wildemberg Luiz Eduardo, Bronstein Marcello D, Gatto Federico, Ferone Diego
Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil.
Neuroendocrinology Section and Molecular Genetics Laboratory, Secretaria Estadual de Saúde do Rio de Janeiro, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
Pituitary. 2017 Feb;20(1):100-108. doi: 10.1007/s11102-017-0791-0.
First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.
第一代生长抑素受体配体（SRL）是肢端肥大症医学治疗的主要手段，然而，在不同研究中，使用这些药物控制病情的患者比例差异显著。对SRL产生耐药性涉及许多因素。在本综述中，我们更新了生长抑素及其受体（sst）的生理学知识、SRL在肢端肥大症治疗中的应用以及与这些药物反应相关的因素。SRL通过与sst相互作用发挥作用，目前已鉴定出sst有五种亚型。第一代SRL，奥曲肽和兰瑞肽，被认为对sst2具有特异性，其生化反应率在20%至70%之间。36%至75%的患者可出现肿瘤体积缩小。几个因素可能决定对这些药物的反应，如生长激素瘤中sst、AIP、E-钙黏蛋白、ZAC1、细丝蛋白A和β-抑制蛋白的表达。对于第一代SRL耐药的患者，替代药物治疗选择包括：SRL高剂量方案、SRL与卡麦角林或培维索孟联合使用，或使用帕西瑞肽。帕西瑞肽是新一代SRL，与sst的相互作用模式更广泛。鉴于肢端肥大症治疗选择最近有所增加，且对当前一线治疗反应决定因素有了更深入的了解，有可能从试错治疗转向个性化治疗。
