Journal Article

Crizotinib in ROS1-Rearranged Non–Small-Cell Lung Cancer

Clark, Jeffrey W, Tan, Weiwei, Zheng, Zongli, Iafrate, A. John, Shaw, Alice T, Ou, Sai-Hong I, Stephenson, Patricia, Shreeve, S. Martin, Salgia, Ravi, Tye, Lesley M, Camidge, D. Ross, Varella-Garcia, Marileila, Wilner, Keith D, Shapiro, Geoffrey I, Costa, Daniel B, Christensen, James G, Le, Long Phi, Riely, Gregory J, Doebele, Robert C, Solomon, Benjamin J, Bang, Yung-Jue

2014

Overview

About 1% of non–small-cell lung cancers have ROS1 rearrangements. This oncogene is inhibited by crizotinib. In a cohort of 50 patients with ROS1 -rearranged lung cancer, crizotinib induced responses in 72%; the median duration of response was nearly a year and a half. The ROS1 oncogene encodes an orphan receptor tyrosine kinase related to anaplastic lymphoma kinase (ALK), along with members of the insulin-receptor family. 1 First discovered as the oncogene product of an avian sarcoma RNA tumor virus, 2 – 4 ROS1 (ROS1 proto-oncogene receptor tyrosine kinase) is activated by chromosomal rearrangement in a variety of human cancers, including non–small-cell lung cancer (NSCLC), cholangiocarcinoma, gastric cancer, ovarian cancer, and glioblastoma multiforme. 5 – 9 Rearrangement leads to fusion of a portion of ROS1 that includes the entire tyrosine kinase domain with 1 of 12 different partner proteins. 10 The resulting ROS1 fusion kinases are constitutively activated and drive . . .

• Publisher: Massachusetts Medical Society
• Subject: Administration, Oral / Adult / Aged / Antitumor activity / Binding sites / Biological and medical sciences / Biomedical research / c-Met protein / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Chromosome rearrangements / Crizotinib / Disease-Free Survival / Enzyme inhibitors / Female / Gene Rearrangement / General aspects / Humans / In Situ Hybridization, Fluorescence / Inhibitor drugs / Kaplan-Meier Estimate / Kinases / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lymphoma / Male / Medical sciences / Middle Aged / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Non-small cell lung carcinoma / Pharmacokinetics / Pneumology / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Protein-tyrosine kinase receptors / Protein-Tyrosine Kinases - genetics / Proto-Oncogene Mas / Proto-Oncogene Proteins - genetics / Pyrazoles - adverse effects / Pyrazoles - therapeutic use / Pyridines - adverse effects / Pyridines - therapeutic use / Targeted cancer therapy / Treatment Outcome / Tumors / Tumors of the respiratory system and mediastinum / Vision Disorders - chemically induced