The resistance mechanisms and treatment strategies of BTK inhibitors in B-cell lymphoma.

Hematological Oncology
Haoran WangKeshu Zhou


Bruton's tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of B-cell lymphoma (BCL). These drugs interfere with the mechanisms underlying malignant B-cell pathophysiology, allowing better drug response as well as low toxicity. However, these multiple mechanisms also lead to drug resistance, which compromised the treatment outcome and needs to be solved urgently. This review focuses on genomic variations (such as BTK and its downstream PCLG2 mutations as well as Del 8p, 2p+, Del 6q/8p, BIRC3, TRAF2, TRAF3, CARD11, MYD88, and CCND1 mutations) and related pathways (such as PI3K/Akt/mTOR, NF-κB, MAPK signaling pathways, overexpression of B-cell lymphoma 6, platelet-derived growth factor, toll-like receptors, and microenvironment, cancer stem cells, and exosomes) involved in cancer pathophysiology to discuss the mechanisms underlying resistance to BTKi. We have also reviewed the newly reported drug resistance mechanisms and the proposed potential treatment strategies (the next-generation BTKi, proteolysis-targeting chimera-BTK, XMU-MP-3, PI3K-Akt-mTOR pathway, MYC or LYN kinase inhibitor, and other small-molecule targeted drugs) to overcome drug resistance. The findings presented in this review lay a strong foundat...Continue Reading


Nov 2, 2001·Nature·T ReyaI L Weissman
Nov 3, 2009·Cell·Lakshmi SrinivasanKlaus Rajewsky
Jul 23, 2011·Genes & Cancer·M Dolores Delgado, Javier León
Nov 24, 2011·British Journal of Haematology·Antònia Obrador-HeviaSilvia Fernández de Mattos
Jun 21, 2013·The New England Journal of Medicine·John C ByrdSusan O'Brien
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sílvia BeàElías Campo
Apr 24, 2014·Seminars in Cancer Biology·William T SenapedisYosef Landesman
May 30, 2014·The New England Journal of Medicine·Jennifer A WoyachJohn C Byrd
Apr 9, 2015·The New England Journal of Medicine·Steven P TreonRanjana H Advani
Apr 11, 2015·British Journal of Haematology·Shuang Q ZhangYue Lynn Wang
Jun 7, 2015·Journal of Hematology & Oncology·Rohit MathurFelipe Samaniego
Jul 21, 2015·Nature Medicine·Wyndham H WilsonLouis M Staudt
Dec 8, 2015·The New England Journal of Medicine·John C ByrdRichard R Furman
Apr 19, 2017·Nature Communications·Xiaohong ZhaoJianguo Tao
Jan 24, 2018·British Journal of Haematology·Oshrat Hershkovitz-RokahOfer Shpilberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.