Potential therapies for anaplastic lymphoma kinase-driven tumors in children: progress to date.
Potential therapies for anaplastic lymphoma kinase-driven tumors in children: progress to date.
复制标题
儿童间变性淋巴瘤激酶驱动肿瘤的潜在疗法：迄今为止的进展。
DOI：
10.1007/s40272-013-0027-3
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Lim,MeganS
中科院分区：
文献类型：
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作者：
Lowe,EricJ;Lim,MeganS
间变性淋巴瘤激酶(ALK)是一种致癌性酪氨酸激酶，在儿童癌症中由于多种分子机制而被解除调控。它们包括染色体易位、激活突变和基因扩增。自1994年首次发现与染色体t(2，5)(p23；q35)易位有关的致癌性酪氨酸激酶以来，已有20多个ALK易位伙伴被鉴定存在于各种癌症中。此外，解除对ALK酪氨酸激酶活性的调节对于其他几种儿科肿瘤的发生至关重要，包括神经母细胞瘤和炎症性肌纤维母细胞瘤。最近在成人肺癌(非小细胞肺癌)患者中发现的ALK易位加速了ALK酪氨酸激酶抑制剂作为治疗药物的发展。虽然在许多患者中观察到了良好的临床反应，但对ALK抑制的临床耐药性的获得突显了开发第二代ALK激酶抑制剂和/或针对下游信号媒介或抗体药物结合物的联合疗法的必要性。本文提供了在儿童人群中ALK驱动的肿瘤的光谱的最新进展，以及针对这些肿瘤的潜在治疗方法。
Anaplastic lymphoma kinase (ALK) is an oncogenic tyrosine kinase that is deregulated due to a variety of molecular mechanisms in pediatric cancer. They include chromosomal translocations, activation mutations, and gene amplifications. Since the initial discovery of ALK as an oncogenic tyrosine kinase involved in the chromosomal translocation t(2, 5)(p23;q35) in 1994, more than 20 translocation partners of ALK have been identified in various cancers. Furthermore, deregulation of ALK tyrosine kinase activity is critical for the pathogenesis of several other pediatric tumors, including neuroblastomas and inflammatory myofibroblastic tumors. The recent discovery of ALK translocations in adult lung cancer patients (non-small cell lung cancer) has accelerated the development of inhibitors of ALK tyrosine kinase as therapeutic agents. While excellent clinical response has been observed in many patients, the acquisition of clinical resistance to ALK inhibition highlights the need for development of second-generation ALK kinase inhibitors and/or combination therapies that target downstream signaling mediators or antibody drug conjugates. This article provides an update on the spectrum of ALK-driven tumors in the pediatric population and the potential therapies which target these tumors.