Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.
Certain malignant B cells rely on B - cell receptor ( BCR)-mediated survival signals . Spleen tyrosine kinase ( Syk ) initiates and amplifies the BCR signal . In in vivo analyses of B - cell lymphoma cell lines and primary tumors , Syk inhibition induces apoptosis . These data prompted a phase 1/2 clinical trial of fostamatinib disodium , the first clinically available oral Syk inhibitor , in patients with recurrent B - cell non - Hodgkin lymphoma ( B - NHL ) . Dose - limiting toxicity in the phase 1 portion was neutropenia , diarrhea , and thrombocytopenia , and 200 mg twice daily was chosen for phase 2 testing . Sixty - eight patients with recurrent B - NHL were then enrolled in 3 cohorts : ( 1 ) diffuse large B - cell lymphoma ( DLBCL ) , ( 2 ) follicular lymphoma ( FL ) , and ( 3 ) other NHL , including mantle cell lymphoma ( MCL ) , marginal zone lymphoma ( MZL ) , mucosa - associated lymphoid tissue lymphoma , lymphoplasmacytic lymphomas , and small lymphocytic leukemia / chronic lymphocytic leukemia ( SLL / CLL ) . Common toxicities included diarrhea , fatigue , cytopenias , hypertension , and nausea . Objective response rates were 22 % ( 5 of 23 ) for DLBCL , 10 % ( 2 of 21 ) for FL , 55 % ( 6 of 11 ) for SLL / CLL , and 11 % ( 1/9 ) for MCL . Median progression - free survival was 4.2 months . Disrupting BCR - induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL / CLL . This trial was registered at www.clinicaltrials.gov as # NCT00446095 .
Which enzyme is inhibited by a drug fostamatinib?
Which enzyme is inhibited by a drug fostamatinib ?
spleen tyrosine kinase
spleen tyrosine kinase