METHODS AND COMPOSITIONS FOR THE DIAGNOSIS AND TREATMENT OF CANCERS RESISTANT TO ROS1 INHIBITORS

摘要

Compositions and methods for the diagnosis and treatment of a cancer that is resistant to at least one ROSl kinase inhibitor are provided herein. The disclosures herein are based on the discovery of mutations within ROSl that confer resistance to at least one ROSl kinase inhibitor. Polynucleotides and polypeptides having at least one ROSl inhibitor resistance mutation are provided and find use in methods and compositions useful in the diagnosis, prognosis, and/or treatment of diseases associated with aberrant ROSl activity, more particularly, those that are resistant to at least one ROSl kinase inhibitor. Methods and compositions are also provided for the identification of agents that can inhibit the kinase activity and/or reduce the expression level of the ROSl kinase inhibitor resistance mutants.