Clinical Activity of Crizotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring ROS1 Gene Rearrangement

摘要

Anew molecular subset of NSCLC is defined by chromosomal rearrangements of the ROS1 receptor tyrosine kinase gene. The ROSl gene encodes a tyrosine kinase receptor, and ROS1 is most closely related to other tyrosine kinases in the insulin receptor super-family. Rearrangements of ROS1 in cell lines lead to expression of ROS1 fusion kinases and sensitivity to the inhibition of ROS kinase. The primary mechanism that activates ROS1 in lung cancer and other cancers is chromosomal rearrangement, and a number of ROS 1 rearrangements can occur in nonsquamous lung cancer. These rearrangements lead to aberrant expression of ROS1 and constitutive activation of its tyrosine kinase.