Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.

ABSTRACT:

Background

Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations in BTK at residue C481, the binding site of covalent BTK inhibitors. Noncovalent (reversible) BTK inhibitors overcome this mechanism and other sources of resistance, but the mechanisms of resistance to these therapies are currently not well understood.

Methods

We performed genomic analyses of pretreatment specimens as well as specimens obtained at the time of disease progression from patients with CLL who had been treated with the noncovalent BTK inhibitor pirtobrutinib. Structural modeling, BTK-binding assay

SUBMITTER: Wang E 

PROVIDER: S-EPMC9074143 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature