Susceptibility of tumors to tyrosine kinase inhibitors and treatment thereof

摘要

This disclosure provides tyrosine kinase protein and nucleic acid variants, particularly FGFR2 variants, which are linked to drug resistance. The disclosure further provides methods of diagnosis and theranosis, using these molecules and fragments thereof, and kits for employing these methods and compositions.

主权项

1. A method for treating a subject having a cancer with amplified or mutationally activated FGFR2 (fibroblast growth factor receptor) kinase, comprising:
receiving a sample from the subject; analyzing the sample for the presence of at least one FGFR2 kinase mutation variant; wherein the subject is drug resistant to one or more FGFR2 kinase inhibitors if one or more FGFR2 kinase mutation variants selected from the group consisting of M536I, M538I, I548V, N550H, N550K, N550S, V565I, E566G, L618M, E719G, and Y770IfsX14 is present in the sample from the subject, wherein the FGFR2 kinase inhibitor is selected from the group consisting of dovitinib, PD173073, AZD4547, ponatinib, BGJ398, and DCC2036; and administering a regimen comprising ponatinib and/or BGJ398 to the subject if at least N550K mutation is present in the patient; or administering a regimen comprising AZD4547 and/or DCC2036 to the subject if at least V565I mutation is present in the subject.