Genomic Alterations of Anaplastic Lymphoma Kinase May Sensitize Tumors to Anaplastic Lymphoma Kinase Inhibitors

摘要: Selective kinase inhibitors have had a substantial impact on the field of medical oncology. Whereas these agents can elicit dramatic clinical responses in some settings, their activity is generally limited to subset treated patients whose tumor cells harbor specific genetic lesion. We established an automated platform for examining sensitivity various molecularly targeted across large panel human tumor-derived cell lines identify additional genotype-correlated that may be clinically relevant. Among tested 602 derived from variety cancers, we found selective inhibitor anaplastic lymphoma (ALK) potently suppressed growth small cells. This included lymphomas, non-small-cell lung and neuroblastomas. ALK receptor tyrosine was first identified as part protein fusion chromosomal translocation detected majority patients, has recently been implicated oncogene fraction cancers Significantly, well correlated with genomic rearrangements, including translocations gene amplification. Moreover, such lines, inhibition lead potent suppression downstream survival signaling apoptotic response. These findings suggest neuroblastomas alterations responsive pharmacologic inhibition.