TY - JOUR
T1 - Ibrutinib resistance in mantle cell lymphoma
T2 - clinical, molecular and treatment aspects
AU - Hershkovitz-Rokah, Oshrat
AU - Pulver, Dana
AU - Lenz, Georg
AU - Shpilberg, Ofer
N1 - Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/5
Y1 - 2018/5
N2 - Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6–10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one-third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.
AB - Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6–10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one-third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.
KW - BCR signalling pathway
KW - ibrutinib resistance
KW - mantle cell lymphoma
KW - resistance mechanism
UR - http://www.scopus.com/inward/record.url?scp=85040762967&partnerID=8YFLogxK
U2 - 10.1111/bjh.15108
DO - 10.1111/bjh.15108
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C2 - 29359797
AN - SCOPUS:85040762967
SN - 0007-1048
VL - 181
SP - 306
EP - 319
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -