B cell signalling pathways-New targets for precision medicine in chronic lymphocytic leukaemia.
Agammaglobulinaemia Tyrosine Kinase
/ antagonists & inhibitors
B-Lymphocytes
/ immunology
Class Ib Phosphatidylinositol 3-Kinase
/ immunology
Enzyme Inhibitors
/ therapeutic use
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Molecular Targeted Therapy
/ methods
Precision Medicine
/ methods
Receptors, Antigen, B-Cell
/ antagonists & inhibitors
Signal Transduction
/ drug effects
B cell receptor signalling
chronic lymphocytic leukaemia
functional precision medicine
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
27
04
2020
revised:
15
06
2020
accepted:
02
07
2020
pubmed:
9
7
2020
medline:
24
11
2020
entrez:
9
7
2020
Statut:
ppublish
Résumé
The B cell receptor (BCR) is a master regulator of B cells, controlling cellular processes such as proliferation, migration and survival. Cell signalling downstream of the BCR is aberrantly activated in the B cell malignancy chronic lymphocytic leukaemia (CLL), supporting the pathophysiology of the disease. This insight has led to development and approval of small molecule inhibitors that target components of the BCR pathway. These advances have greatly improved the management of CLL, but the disease remains incurable. This may partly be explained by the inter-patient heterogeneity of the disease, also when it comes to treatment responses. Precision medicine is therefore required to optimize treatment and move towards a cure. Here, we discuss how the introduction of BCR signalling inhibitors has facilitated the development of functional in vitro assays to guide clinical treatment decisions on use of the same therapeutic agents in individual patients. The cellular responses to these agents can be analysed in high-throughput assays such as dynamic BH3 profiling, phospho flow experiments and drug sensitivity screens to identify predictive biomarkers. This progress exemplifies the positive synergy between basal and translational research needed to optimize patient care.
Substances chimiques
Enzyme Inhibitors
0
Receptors, Antigen, B-Cell
0
Class Ib Phosphatidylinositol 3-Kinase
EC 2.7.1.137
PIK3CG protein, human
EC 2.7.1.137
Agammaglobulinaemia Tyrosine Kinase
EC 2.7.10.2
BTK protein, human
EC 2.7.10.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12931Subventions
Organisme : Stiftelsen Kristian Gerhard Jebsen
Organisme : Norges Forskningsråd
Organisme : Kreftforeningen
Organisme : Lilly Constance og Karl Ingolf Larssons stiftelse
Organisme : Helse Sør-Øst RHF
Informations de copyright
© 2019 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.
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