Mutational analysis in XXXX : when and what to do?

@entity1 @entity2213 @entity28837 @entity1860
PURPOSE OF REVIEW: @entity2213 , which was the first targeted therapy for @entity1 with @entity1860 ( @entity1860 ), has led to the significant prolongation of life for most @entity1 . However, approximately 30% fail therapy. The major mechanism of acquired resistance is somatic mutation within the BCR-ABL1 kinase domain, which affects @entity2213 binding. Recently, more potent inhibitors have been approved that retain activity against most of the more than 100 mutations. However, some mutations remain problematic for one or more of the new inhibitors. The most frequently detected mutation, @entity28837 , remains resistant to all of the currently approved inhibitors. More sensitive mutation techniques that focus on the detection of a limited number of specific mutations may be beneficial, but are yet to prove their clinical utility for the early detection of relapse in routine practice. RECENT FINDINGS: Inhibitors with alternate binding modes that may overcome @entity28837 -associated resistance are at the preclinical stage or are undergoing clinical trial. SUMMARY: Each of the new, more potent kinase inhibitor drugs appear to have a partially overlapping set of mutations that confer a degree of resistance. Mutation detection techniques may need to adapt to provide clinicians with a more timely indication of mutation acquisition and pending relapse.
