The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm

Don L. Gibbons; Sabrina Pricl; Hagop Kantarjian; Jorge Cortes; Alfonso Quintás-Cardama

doi:10.1002/cncr.26225

The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm

Don L. Gibbons, Sabrina Pricl, Hagop Kantarjian, Jorge Cortes, Alfonso Quintás-Cardama

Research output: Contribution to journal › Comment/debate › peer-review

68 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	293-299
Number of pages	7
Journal	Cancer
Volume	118
Issue number	2
DOIs	https://doi.org/10.1002/cncr.26225
State	Published - Jan 15 2012
Externally published	Yes

Keywords

Chronic myeloid leukemia
Gatekeeper mutation
Ponatinib
Threonine-to-isoleucine mutation at codon 315
Tyrosine kinase inhibitor

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cncr.26225

Cite this

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title = "The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm",

abstract = "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.",

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AU - Gibbons, Don L.

AU - Pricl, Sabrina

AU - Kantarjian, Hagop

AU - Cortes, Jorge

AU - Quintás-Cardama, Alfonso

PY - 2012/1/15

Y1 - 2012/1/15

N2 - 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.

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The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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