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个体化治疗肢端肥大症中的培高利特。

Pasireotide in the Personalized Treatment of Acromegaly.

机构信息

Endocrinology & Nutrition Service, Germans Trias Hospital and Research Institute, Badalona, Autonomous University of Barcelona, Badalona, Spain.

Endocrinology & Nutrition Service, Complejo Universitario de Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

Front Endocrinol (Lausanne). 2021 Mar 16;12:648411. doi: 10.3389/fendo.2021.648411. eCollection 2021.

Abstract

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low and high expression of , low or mutated condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

摘要

对于第一代生长抑素受体配体(第一代 SRL)一线治疗无反应的患者,疾病控制的延迟可以用年来衡量,因为每次对药物治疗的调整都需要几个月的时间才能得到充分评估。考虑到这一点,通过使用识别药物反应的生物标志物,肢端肥大症的治疗应该受益于个性化医学治疗方法。培高利特主要被定位为一种用于第一代 SRL 耐药患者和手术失败后的药物,但现在有足够的数据表明,它是具有某些特征的患者的一线治疗药物。培高利特已被证明对 T2 MRI 信号高信号的患者以及表达低和高、低或突变、稀疏颗粒状免疫组织化学模式的患者有用。这种临床和病理特征的组合对于某些患者是独特的,似乎聚集在同一病例中,强烈提示存在病因学联系。因此,在本文中,我们建议将这种临床病理表型纳入治疗算法中,这将使我们能够使用具有最大潜力实现 GH 分泌过度最快控制以及肿瘤缩小积极效果的药物作为一线治疗,从而加速肢端肥大症的精准医学的实施。此外,我们建议开发、验证和临床应用培高利特急性试验,以识别对培高利特 LAR 有反应的患者,就像奥曲肽急性试验能够对 SRL 所做的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce3/8008639/8ec9870735ca/fendo-12-648411-g001.jpg

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