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B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies.
- Source :
-
International reviews of immunology [Int Rev Immunol] 2013 Aug; Vol. 32 (4), pp. 397-427. - Publication Year :
- 2013
-
Abstract
- B-cell receptor (BCR) signaling is essential for normal B-cell development, selection, survival, proliferation, and differentiation into antibody-secreting cells. Similarly, this pathway plays a key role in the pathogenesis of multiple B-cell malignancies. Genetic and pharmacological approaches have established an important role for the Spleen tyrosine kinase (Syk), Bruton's tyrosine kinase (Btk), and phosphatidylinositol 3-kinase isoform p110delta (PI3Kδ) in coupling the BCR and other BCRs to B-cell survival, migration, and activation. In the past few years, several small-molecule inhibitory drugs that target PI3Kδ, Btk, and Syk have been developed and shown to have efficacy in clinical trials for the treatment of several types of B-cell malignancies. Emerging preclinical data have also shown a critical role of BCR signaling in the activation and function of self-reactive B cells that contribute to autoimmune diseases. Because BCR signaling plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, inhibition of this pathway may represent a promising new strategy for treating these diseases. This review summarizes recent achievements in the mechanism of action, pharmacological properties, and clinical activity and toxicity of these BCR signaling inhibitors, with a focus on their emerging role in treating lymphoid malignancies and autoimmune disorders.
- Subjects :
- B-Lymphocytes physiology
Humans
Antineoplastic Agents therapeutic use
Autoimmune Diseases drug therapy
Autoimmune Diseases metabolism
Leukemia, B-Cell drug therapy
Leukemia, B-Cell metabolism
Lymphoma, B-Cell drug therapy
Lymphoma, B-Cell metabolism
Receptors, Antigen, B-Cell metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1563-5244
- Volume :
- 32
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International reviews of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23886342
- Full Text :
- https://doi.org/10.3109/08830185.2013.818140