研究生长抑素类似物pasireotide (SOM230)在神经内分泌疾病治疗中的潜在作用

L. Nachtigall, B. Biller
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引用次数: 2

摘要

许多神经内分泌肿瘤表达多种生长抑素受体亚型,生长抑素类似物被用于医学治疗。pasireotide (SOM230)是一种具有多配体特性的新型生长抑素类似物,可能为这些肿瘤提供新的潜在治疗方法。本文综述了pasireotide (SOM230)的体外、动物和早期人体临床研究。生长抑素类似物,如lanreotide和octreotide,对许多患者有效,但超过三分之一的肢端肥大症患者无法实现生化控制,而在类癌患者中,长期使用后症状可能变得难治性。Pasireotide与生长抑素受体(1、2、3和5)的五种亚型中的四种具有高亲和力结合,可能控制激素过度分泌或肿瘤增殖。生长抑素受体-5似乎在调节促肾上腺皮质激素分泌中起重要作用,提示pasireotide可能用于库欣病。pasireotide在肢端肥大症,库欣病和类癌中的II期研究的初步结果被提出。短期、小型的临床研究表明,pasireotide用于肢端肥大症和垂体库欣症以及缓解难治性类癌的症状是有希望的。进一步的研究将确定pasireotide对于治疗神经内分泌疾病中的激素过量、临床症状或肿瘤增殖是否有效和安全。
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The potential role of the investigational somatostatin analog pasireotide (SOM230) in the treatment of neuroendocrine disorders
Purpose of reviewMany neuroendocrine tumors express a variety of somatostatin receptor subtypes and somatostatin analogues are used in medical treatment. The development of pasireotide (SOM230), a novel somatostatin analogue with multiligand properties, may offer a new potential therapy for these tumors. This review considers in-vitro, animal and early human clinical studies of pasireotide (SOM230). Recent findingsSomatostatin analogues, such as lanreotide and octreotide, are effective in many patients, but biochemical control is not achieved in over one third of patients with acromegaly, and in carcinoid, symptoms may become refractory after chronic use. Pasireotide, with high affinity binding to four of the five subtypes of somatostatin receptors (1, 2, 3, and 5) may control hormone oversecretion or tumor proliferation. Somatostatin receptor-5 appears to be important in regulating adrenocorticotropic hormone secretion, suggesting the possible use of pasireotide in Cushing's disease. Preliminary results from phase II studies of pasireotide in acromegaly, Cushing's, and carcinoid are presented. SummaryShort-term, small clinical studies using pasireotide for acromegaly and pituitary Cushing's and for symptomatic relief in refractory carcinoid are promising. Further investigation will determine whether pasireotide will be effective and safe for treating hormone excess, clinical symptoms or tumor proliferation in neuroendocrine disorders.
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