Targeting B cell receptor signalling in cancer: preclinical and clinical advances
Abstract
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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BTK is a non-receptor tyrosine kinase that amplifies upstream BCR signaling and is essential for B-cell development and maturation.
“Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase that amplifiesupstream B-cell receptor (BCR) signaling and is essential for B-cell development and maturation(1, 2).”
From Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy (2025) · cites this paper as [2]
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Role of Bruton’s tyrosine kinase in B cells and malignancies
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Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma
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Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy
Gruessner, C., Wiestner, A., & Sun, C. (2025) · Leukemia & Lymphoma · doi:10.1080/10428194.2025.2466101 · Cited by 6 · see citing works
“…is a non-receptor tyrosine kinase that amplifies upstream B-cell receptor (BcR) signaling and is essential for B-cell development and maturation [1,2]. in normal B cells, BtK activation leads to activation of nuclear factor kappa B (NF-κB) enabling increased B-cell survival and proliferation…”
Self-citation
- Authors
- Burger, J. A., & Wiestner, A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- National Institutes of Health (US)
- Corresponding author
- Burger, Jan A.
- Venue
- Nature Reviews Cancer
- Published
- 2018-01-19
- Volume
- 18
- Issue
- 3
- Pages
- 148-167
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2782689871
- Cited by
- 431
- References
- 14
- Citations by year
- 2026: 43 · 2025: 51 · 2024: 58 · 2023: 57 · 2022: 70 · 2021: 63 · 2020: 40 · 2019: 28 · 2018: 20
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- B cell receptor signaling, B-cell malignancies, B-cell leukemia, B-cell lymphoma, BTK inhibitors, tumor microenvironment, squamous cell carcinoma, pancreatic cancer, kinase inhibitors
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Antineoplastic Agents, B-Lymphocytes, Humans, Neoplasms, Receptors, Antigen, B-Cell, Signal Transduction, Leukemia, Lymphocytic, Chronic, B-Cell, Drug Resistance, Neoplasm, Lymphoma, Mantle-Cell, Protein Kinase Inhibitors, Molecular Targeted Therapy, Tumor Microenvironment
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