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
In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death
Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes.
Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling
ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia.
Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell anti-tumor activity.
Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma
The bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach
The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia
PD-L1 checkpoint blockade prevents immune dysfunction and leukemia development in a mouse model of chronic lymphocytic leukemia.
Hypermorphic mutation of phospholipase C, γ2 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation.
Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.
A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.
Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy
Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials
Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition
Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations
LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia
Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial
Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study
Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression by Blocking BCR-Dependent and -Independent Activation of NF-κB and AKT
Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells
Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study.
Microenvironmental agonists generate de novo phenotypic resistance to combined ibrutinib plus venetoclax in CLL and MCL
Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition
Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice
CD40L mediated alternative NFκB-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma.
Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience.
Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment
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 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.