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CHRONIC LYMPHOCYTIC-LEUKEMIA;; CHRONIC MYELOID-LEUKEMIA;; ACQUIRED-RESISTANCE;; CLINICAL RESISTANCE;; THERAPEUTIC TARGET;; ANTIGEN;; RECEPTOR;; POINT MUTATIONS;; GENE MUTATION;; CANCER;; PCI-32765;; Medicine
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Full-Text Articles in Medicine and Health Sciences
Resistance Mechanisms For The Bruton's Tyrosine Kinase Inhibitor Ibrutinib, J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka, A. S. Ruppert, L. Xue, D. H. H. Li, J. C. Barrientos, J. C. Byrd, +15 Additional Authors
Resistance Mechanisms For The Bruton's Tyrosine Kinase Inhibitor Ibrutinib, J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka, A. S. Ruppert, L. Xue, D. H. H. Li, J. C. Barrientos, J. C. Byrd, +15 Additional Authors
Journal Articles
BACKGROUND Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. METHODS We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. …