Voena Claudia, Peola Silvia, Chiarle Roberto
Department of Pathology, Children's Hospital Boston, Associate Professor in Pathology, Harvard Medical School, Enders 1116.1., 300 Longwood Ave, Boston, MA 02115,
Front Biosci (Schol Ed). 2015 Jun 1;7(2):269-82. doi: 10.2741/S440.
Twenty years ago anaplastic lymphoma kinase (ALK) was discovered in anaplastic large cell lymphoma (ALCL), but the interest in ALK as an oncogene grew only in recent years when ALK rearrangements were reported as recurrent genetic lesions in lung carcinoma and activating single point mutations were described in neuroblastoma. In this review we will describe the main features of ALK-rearranged solid tumors, with particular emphasis to NSCLC and neuroblastoma. We will discuss the numerous in vitro and in vivo studies that confirmed ALK as the driver oncogene in these tumors and the achievements in clinical settings with ALK inhibitors that validated ALK as a therapeutic target. We will finally end with the description of putative innovative therapeutic approaches that are on going to overcome acquired resistance that invariably occurs in crizotinib treated NSCLC patients or intrinsic resistance to crizotinb therapy reported in neuroblastoma.
二十年前，间变性淋巴瘤激酶（ALK）在间变性大细胞淋巴瘤（ALCL）中被发现，但直到近年来，当ALK重排在肺癌中被报道为复发性基因病变且在神经母细胞瘤中发现了激活单点突变时，人们对ALK作为一种致癌基因的兴趣才开始增加。在这篇综述中，我们将描述ALK重排实体瘤的主要特征，尤其着重于非小细胞肺癌（NSCLC）和神经母细胞瘤。我们将讨论众多的体外和体内研究，这些研究证实了ALK是这些肿瘤中的驱动致癌基因，以及使用ALK抑制剂在临床环境中所取得的成果，这些成果验证了ALK作为治疗靶点的地位。最后，我们将描述正在进行的一些假定的创新治疗方法，这些方法旨在克服克唑替尼治疗的NSCLC患者中不可避免出现的获得性耐药性或神经母细胞瘤中报道的对克唑替尼治疗的固有耐药性。
