Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Room Ee530b, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Endocr Relat Cancer. 2011 Dec 1;18(6):R233-51. doi: 10.1530/ERC-10-0334. Print 2011 Dec.
Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D(2) receptor (D(2)) have been demonstrated to be effective in controlling hormone secretion and cell proliferation in in vivo and in vitro studies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D(2) as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D(2) pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.
生长抑素 (SS) 和多巴胺 (DA) 受体已被强调为广泛的人类内分泌肿瘤中激素分泌负调控的两个关键调节剂。这两种受体家族都属于 G 蛋白偶联受体超家族，具有许多结构和功能特征。由于神经内分泌肿瘤 (NET) 中通常报道的生长抑素受体 (SSTR) 高表达，生长抑素类似物 (SSA) 在该类肿瘤的医学治疗中具有显著作用，尤其是垂体腺瘤和分化良好的胃肠胰腺神经内分泌肿瘤 (GEP NET)。此外，NET 不仅表达 SSTR，而且还经常表达多巴胺受体 (DR)，并且已经证明靶向 D2 受体 (D2) 的 DA 激动剂在体内和体外研究中有效控制激素分泌和细胞增殖。SSA 联合 DA 激动剂的治疗已在 GH 分泌性垂体腺瘤的亚组患者中证明有效，并且在少数类癌病例中也有报道。新的选择性和通用 SSA 和 DA 激动剂以及 SS/DA 嵌合化合物的最近可用性，可能为 SSTR 和 D2 作为 NET 生物治疗的联合靶标提供新的见解。本文综述了评估 NET 中 SSTR 和 DR 表达的最新研究，重点关注它们的共表达及其共表达的可能临床意义。此外，还讨论了 SSTR 和 D2 的最新病理生理学见解以及使用 SSA、DA 激动剂和 SS/DA 嵌合化合物治疗的未来前景。
