The role of ALK in human neoplasia

The role of ALK in human neoplasia

George Karagkounis, Christos Masaoutis, Theodore Argyrakos, Dimitra Rontogianni, George Stranjalis, Damianos Sakas, Dina Tiniakos


ALK (Anaplastic Lymphoma Kinase) protein belongs to the receptor tyrosine kinase (RTK) family and is normally involved in multiple signaling pathways regulating various cellular functions. Since the first report of a chromosomal translocation involving an alk locus in anaplastic large cell lymphoma (ALCL), ALK has been studied in many other human neoplasms. Multiple alterations of the alk gene have been discovered, such as point mutations, multiple gene copies (neuroblastoma), translocations (TPM-ALK positive inflammatory myofibroblastic tumors, IMTs) and inversions [EML4-ALK positive non-small cell lung carcinomas (NSCLC)]. The fusion proteins formed from gene translocations can lead to activation and up-regulation of ALK-related signaling pathways, resulting in uncontrolled cell proliferation and neoplastic growth. RTKs such as ALK have become attractive targets for the development of targeted therapies. RTK inhibitors of the 1st (such as Crizotinib) and 2nd  generation are already in use in selected NSCLC, IMT and ALCL cases, and one of the goals in modern oncology is to expand their application for the treatment of many other neoplasms in the near future. In this review, we present data on the alk gene, protein and ligands, molecular pathways it relates to, and pathological expression in ALK-related malignancies.


ALK, cancer, carcinoma, neoplasia, receptor tyrosine kinases, inversion, translocation, signaling pathway, proliferation, prognosis

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