Coluccia A M L, Gunby R H, Tartari C J, Scapozza L, Gambacorti-Passerini C, Passoni Lorena
Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Expert Opin Ther Targets. 2005 Jun;9(3):515-32. doi: 10.1517/14728222.9.3.515.
A crucial issue in the development of molecularly-targeted anticancer therapies is the identification of appropriate molecules whose targeting would result in tumour regression with a minimal level of systemic toxicity. Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase, normally expressed at low levels in the nervous system. As a consequence of chromosomal translocations involving the alk gene (2p23), ALK is also aberrantly expressed and constitutively activated in approximately 60% of CD30+ anaplastic large cell lymphomas (ALCLs). Due to the selective overexpression of ALK in tumour cells, its direct involvement in the process of malignant transformation and its frequent expression in ALCL patients, the authors recognise ALK as a suitable candidate for the development of molecularly targeted strategies for the therapeutic treatment of ALK-positive lymphomas. Strategies targeting ALK directly or indirectly via the inhibition of the protein networks responsible for ALK oncogenic signalling are discussed.
分子靶向抗癌疗法发展中的一个关键问题是确定合适的分子，其靶向作用能使肿瘤消退，同时全身毒性水平降至最低。间变性淋巴瘤激酶（ALK）是一种跨膜受体酪氨酸激酶，通常在神经系统中低水平表达。由于涉及alk基因（2p23）的染色体易位，ALK在大约60%的CD30 + 间变性大细胞淋巴瘤（ALCL）中也异常表达并持续激活。由于ALK在肿瘤细胞中选择性过表达，其直接参与恶性转化过程且在ALCL患者中频繁表达，作者认为ALK是开发针对ALK阳性淋巴瘤的分子靶向治疗策略的合适候选分子。本文讨论了直接或间接通过抑制负责ALK致癌信号的蛋白质网络来靶向ALK的策略。
