E-mail a Wiley Online Library Link

Don L. Gibbons, Sabrina Pricl, Hagop Kantarjian, Jorge Cortes and Alfonso Quintás-Cardama The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm Cancer 118

Article first published online: 5 JUL 2011 | DOI: 10.1002/cncr.26225

Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid leukemia (CML). However, the development of resistance breakpoint cluster region/Abelson murine leukemia 1 (BCR-ABL1) mutations impair their activity. The gatekeeper threonine-to-isoleucine mutation at codon 315 (T315I) produces complete insensitivity to all currently approved TKIs in CML. Other mutated gatekeeper residues in a variety of oncogenic kinases that drive the pathogenesis of different human cancers have proven highly resistant to TKI therapy. Advances in the structural biology of oncogenic kinases have facilitated the rational development of TKIs that are active against gatekeeper mutations, which are exemplified best by ponatinib in CML.

Complete the form below and we will send an e-mail message containing a link to the selected article on your behalf

Required = Required Field

Choose captcha format: Image or Audio. Click here if you need help.