Work

Strategies to circumvent the T315I gatekeeper mutation in the Bcr-Abl tyrosine kinase

Year: 2013

Type: article

Abstract: Despite the remarkable success of imatinib against Bcr-Abl, development of secondary resistance, most often due to point mutations in the Bcr-Abl tyrosine kinase (TK) domain, is quite common. Of these, the T315I "gatekeeper" mutation is resistant to all currently registered Bcr-Abl TK inhibitors (TKIs) with the notable exception of ponatinib (Iclusig™), which was very recently approved by the United States Food and Drug Administration (FDA). Besides ponatinib, numerous strategies have been developed to circumvent this problem. These include the protein synthesis inhibitor omacetaxine (Synribo®), and "switch-control" inhibitors. Dual Bcr-Abl and aurora kinase inhibitors represent another promising strategy. Finally, several promising synergistic combinations, such as TKIs with histone deacetylase inhibitors (HDACIs), warrant attention.

Source: Leukemia Research Reports

DOI: 10.1016/j.lrr.2013.02.001

Authors: Prithviraj Bose, Haeseong Park, Jawad Al-Khafaji, Steven Grant

Institutions: Virginia Commonwealth University, VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University Medical Center

Language: English

Topic: Chronic Myeloid Leukemia Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,180