Bruton's tyrosine kinase inhibitors in B-cell non-Hodgkin's lymphomas.

Abstract

The B-cell receptor pathway (BCR) is aberrantly activated in select B-cell malignancies. This knowledge has allowed for the development of inhibitors of different crucial steps of this pathway. Bruton's tyrosine kinase (BTK) is a key component of BCR signaling and functions as an important regulator of multiple cell functions including differentiation, proliferation, and survival in various B-cell malignancies. Ibrutinib is a potent, selective BTK inhibitor that has shown significant activity in specific subtypes of B-cell non-Hodgkin's lymphomas (NHLs). Given the high response rates, tolerability, and acceptable toxicities, ibrutinib was recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed mantle cell lymphoma and chronic lymphocytic leukemia. It is also currently being evaluated in combination with chemotherapy and as frontline therapy in B-cell NHL. This review summarizes the preclinical and clinical development of ibrutinib in the treatment of B-cell NHL.

• Authors: L Alinari, C Quinion, K A Blum
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 97 Issue 5 Pg. 469-77 (May 2015) ISSN: 1532-6535 [Electronic] United States
• PMID: 25670208 (Publication Type: Journal Article, Review)
• Copyright: © 2015 American Society for Clinical Pharmacology and Therapeutics.

Chemical References

• Antineoplastic Agents
• Piperidines
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• ibrutinib
• Protein-Tyrosine Kinases
• Agammaglobulinaemia Tyrosine Kinase
• BTK protein, human
• Adenine

Topics

• Adenine (analogs & derivatives)
• Agammaglobulinaemia Tyrosine Kinase
• Animals
• Antineoplastic Agents (therapeutic use)
• Drug Discovery
• Humans
• Lymphoma, B-Cell (drug therapy, enzymology, genetics, pathology)
• Molecular Targeted Therapy
• Piperidines
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors, genetics, metabolism)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Signal Transduction (drug effects)
• Treatment Outcome