TY - JOUR
T1 - Targeting B cell receptor signalling in cancer
T2 - Preclinical and clinical advances
AU - Burger, Jan A.
AU - Wiestner, Adrian
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrc.2017.121
DO - 10.1038/nrc.2017.121
M3 - Review article
C2 - 29348577
AN - SCOPUS:85042141050
SN - 1474-175X
VL - 18
SP - 148
EP - 167
JO - Nature Reviews Cancer
JF - Nature Reviews Cancer
IS - 3
ER -