Tyrosine kinase gene rearrangements in epithelial malignancies.

Tyrosine kinase gene rearrangements in epithelial malignancies.
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DOI:
10.1038/nrc3612
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发表时间:
2013-11
期刊:
Nature reviews. Cancer
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其他
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在许多上皮癌中观察到导致致癌激酶激活的染色体重排。这些癌症表达激活的融合激酶,驱动恶性肿瘤的发生和进展,并且通常对小分子激酶抑制剂有相当大的反应,这验证了这些融合激酶作为“可药物”靶标。在这篇综述中,我们研究了与含有致癌融合激酶的癌症相关的病因、致病和临床特征,包括间变性淋巴瘤激酶 (ALK)、ROS1 和 RET。我们讨论了靶向治疗的临床结果,并探索了发现实体瘤中染色体重排激活的其他激酶的策略。
Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.
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