Erdafitinib 治疗期间的线性生长加速:与表皮生长因子受体相关,但与生长因子和性激素无关的机制?

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Adalbert Raimann, Natalia Stepien, Amedeo A Azizi, Gabriele Hartmann, Johannes Gojo
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引用次数: 0

摘要

导言:出生后的生长加速只发生在青春期,这是一种生理现象,也发生在生长障碍患者接受生长促进疗法后的追赶性生长过程中。在此,我们报告了在使用酪氨酸激酶抑制剂 Erdafitinib(TKI)治疗期间对骨骼症状的新观察:对中枢神经系统肿瘤患者的人体测量学、生化、临床和放射学数据进行了回顾性分析,这些患者在开始接受厄达非替尼治疗时出现了意料之外的生长突增:线性生长加速与性类固醇和IGF1水平无关,这在接受大量预处理的儿科神经肿瘤患者中尤为显著,因为这些患者在开始治疗前存在严重的生长障碍。在开始接受TKI治疗后不久,生长加速伴随着生长板明显增宽和骺板矿化增强:尽管包括TKIs在内的靶向疗法已成为成人癌症治疗的重要组成部分,但在儿童中的应用仍然有限。在各种器官系统中都观察到了儿童特有的非靶向效应,但有关TKIs对生长中骨骼的影响的知识却很少。Erdafitinib 可抑制表皮生长因子受体 3 介导的效应,因此是生长因子和性激素独立生长加速的一个非常合理的假设框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Accelerated Linear Growth during Erdafitinib Treatment: An FGFR-Related, but Growth Factor and Sex Steroid-Independent Mechanism?

Introduction: Growth acceleration during postnatal growth only occurs during puberty as a physiological event and during catch-up growth mediated by growth-promoting therapies in growth disorders. Here we report on novel observations of skeletal symptoms during treatment with erdafitinib, a tyrosine kinase inhibitor (TKI) prescribed on the basis of a compassionate-use program.

Methods: Analysis of anthropometric, biochemical, clinical, and radiographic data of patients with CNS tumors who revealed an unanticipated growth spurt with initiation of therapy with erdafitinib was performed retrospectively.

Results: Linear growth acceleration was independent of sex steroids and IGF1 levels, which is especially remarkable in the context of heavily pretreated pediatric neuro-oncology patients with severe growth impairment before initiation of therapy. Growth acceleration was accompanied by a distinct widening of the growth plate and enhanced metaphyseal mineralization shortly after the start of TKI therapy.

Conclusions: While targeted therapies including TKIs have become an essential part of adult cancer treatment, applications in children are still limited. Off-target effects specific to the pediatric population have been observed in various organ systems; however, knowledge about the effect of TKIs on the growing skeleton is scarce. Treatment with erdafitinib inhibits FGFR3-mediated effects and thus represents a very logical hypothetical framework of growth factor and sex steroid-independent growth acceleration.

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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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