Premium
The rise and fall of gatekeeper mutations? The BCR‐ABL1 T315I paradigm
Author(s) -
Gibbons Don L.,
Pricl Sabrina,
Kantarjian Hagop,
Cortes Jorge,
QuintásCardama Alfonso
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26225
Subject(s) - imatinib mesylate , medicine , cancer research , tyrosine kinase , mutation , imatinib , kinase , cancer , genetics , biology , gene , myeloid leukemia , receptor
The use of tyrosine kinase inhibitors (TKIs) has become an integral component of cancer therapy. Imatinib mesylate, a breakpoint cluster region‐Abelson BCR‐ABL1 inhibitor, was the first TKI approved in cancer medicine and has served as a model for the development of similar agents for other cancers. An important drawback of TKI therapy is the development of resistance, frequently through the acquisition of mutations. Mutations at the gatekeeper residues of BCR‐ABL1 (eg, the threonine‐to‐isoleucine mutation at codon 315) and other oncogenic kinases have proven highly resistant to currently available TKIs. Advances in the structural biology of oncogenic kinases have facilitated the rational development of TKIs that are active against gatekeeper mutations. Cancer 2011;. © 2011 American Cancer Society.