METHODS OF TREATING CANCERS CHARACTERIZED BY ABERRENT ROS1 ACTIVITY

摘要

Disclosed herein are methods of treating cancers characterized by aberrant ROS1 activity by administering an effective amount of foretinib (N1′-[3-fluoro-4-[[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide), including methods of identifying mutations in the kinase domain of ROS1 that indicate resistance to crizotinib, but sensitivity to foretinib.

主权项

1. A method of treating a subject with a cancer characterized by aberrant ROS-1 activity, the method comprising:
receiving a sample comprising a cancer cell from the subject; isolating a nucleic acid from the sample, wherein the nucleic acid includes a nucleic acid sequence that encodes SEQ ID NO: 1; identifying a mutation in the nucleic acid encoding SEQ ID NO: 1 that results in an amino acid substitution in G2032, V2098, G1971, L1982, C2050, L1947, or E1935 wherein the presence of one or more of the mutations identifies the sample as comprising a crizotinib resistant and foretinib sensitive cancer cell; and treating the subject with foretinib.