Journal Article

Targeting B cell receptor signalling in cancer: preclinical and clinical advances

Burger, Jan A, Wiestner, Adrian

2018

Overview

B cell receptor (BCR) signalling is crucial for normal B cell development and adaptive immunity. BCR signalling also supports the survival and growth of malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism of BCR pathway activation in these diseases includes continuous BCR stimulation by microbial antigens or autoantigens present in the tissue microenvironment, activating mutations within the BCR complex or downstream signalling components and ligand-independent tonic BCR signalling. The most established agents targeting BCR signalling are Bruton tyrosine kinase (BTK) inhibitors and PI3K isoform-specific inhibitors, and their introduction into the clinic is rapidly changing how B cell malignancies are treated. B cells and BCR-related kinases, such as BTK, also play a role in the microenvironment of solid tumours, such as squamous cell carcinoma and pancreatic cancer, and therefore targeting B cells or BCR-related kinases may have anticancer activity beyond B cell malignancies.

• Publisher: Nature Publishing Group
• Subject: 1-Phosphatidylinositol 3-kinase / Adaptive immunity / Anoikis / Antitumor activity / Apoptosis / Autoantigens / B-cell receptor / Beta cells / Bruton's tyrosine kinase / Cell activation / Cell death / Cell differentiation / Chemokine receptors / Chemotherapy / Chronic lymphocytic leukemia / Clinical trials / Homing receptors / Integrins / Itk protein / Kinases / Leukemia / Lymphocyte receptors / Lymphocytes T / Lymphoma / Macrophages / Mantle cell lymphoma / Microenvironments / Monocytes / Mutation / Neoplasia / Pancreatic cancer / Pancreatic carcinoma / Patients / Peripheral blood / Protein-tyrosine kinase / Receptor mechanisms / Signal transduction / Solid tumors / Spleen / Squamous cell carcinoma / T cell receptors