ros1基因介绍以及未来探讨

1、ROS1ROS1ROS1 is a receptor tyrosine kinase (RTK) of the insulin receptor family. Chromosomal rearrangements involving the ROS1 gene, on chromosome 6q22, were originally described in glioblastomas The location of the ROS1 geneThe ROS1 gene is located on the long (q) arm of chromosome 6 at position 22

2、.Normal function of the ROS1This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may func

3、tion as a growth or differentiation factor receptor. J. Acquaviva et al. / Biochimica et Biophysica Acta 1795 (2009) 3752May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. signaling p

4、athway of the ROS1 NSCLC and the lung cancerAbnormalities in in the ROS1 gene can lead to a type of lung cancer known as non-small cell lung cancer (NSCLC). About 1% to 2% of individuals with NSCLC have an abnormality in which the ROS1 gene is fused to parts of another gene.Diagnostic for ROS11.FISH

5、(荧光原位杂交)2.RT-PCR(逆转录聚合酶链式反应)3. IHC(免疫组织化学染色)ROS1 FISHThe ROS1 FISH test is recommended for screening NSCLC cases that are negative for EGFR mutation and ALK fusion.http:/ & ALKROS1 is evolutionarily related to ALK.Although ROS1 shares only 49% amino acid sequence homology with ALK in the kinase

6、domains, several ALK inhibitors have demonstrated in vitro inhibitory activity against ROS1 . ROS1ALKALK inhibitorsCrizotinib (Xalkori)（克唑替尼克唑替尼）ceritinib (Zykadia) （色瑞替尼） The U.S. Food and Drug Administration (FDA) has not yet approved any drugs that directly target the ROS1 biomarker. However, clinical trials have shown promising effects for patients with ROS1 mutations who are treated with the ROS1 inhibitor crizotinib (Xalkori). The current National Comprehensive Cancer Network (NCCN) guidelines suggest crizotinib therapy in patients with advanced NSCLC bearing aROS1rear