Matches in SemOpenAlex for { <https://semopenalex.org/work/W2895844167> ?p ?o ?g. }
- W2895844167 endingPage "1184" @default.
- W2895844167 startingPage "1174" @default.
- W2895844167 abstract "Abstract Purpose: Preclinical studies suggest SYK and JAK contribute to tumor-intrinsic and microenvironment-derived survival signals. The pharmacodynamics of cerdulatinib, a dual SYK/JAK inhibitor, and associations with tumor response were investigated. Patients and Methods: In a phase I dose-escalation study in adults with relapsed/refractory B-cell malignancies, cerdulatinib was administered orally to sequential dose-escalation cohorts using once-daily or twice-daily schedules. The study enrolled 8 patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), 13 with follicular lymphoma, 16 with diffuse large B-cell lymphoma (DLBCL), and 6 with mantle cell lymphoma. Correlation of tumor response with pharmacodynamic markers was determined in patients with meaningful clinical responses. Results: Following cerdulatinib administration, complete SYK and JAK pathway inhibition was achieved in whole blood of patients at tolerated exposures. Target inhibition correlated with serum cerdulatinib concentration, and IC50 values against B-cell antigen receptor (BCR), IL2, IL4, and IL6 signaling pathways were 0.27 to 1.11 μmol/L, depending on the phosphorylation event. Significant correlations were observed between SYK and JAK pathway inhibition and tumor response. Serum inflammation markers were reduced by cerdulatinib, and several significantly correlated with tumor response. Diminished expression of CD69 and CD86 (B-cell activation markers), CD5 (negative regulator of BCR signaling), and enhanced expression of CXCR4 were observed in 2 patients with CLL, consistent with BCR and IL4 suppression and loss of proliferative capacity. Conclusions: Cerdulatinib potently and selectively inhibited SYK/JAK signaling at tolerated exposures in patients with relapsed/refractory B-cell malignancies. The extent of target inhibition in whole-blood assays and suppression of inflammation correlated with tumor response. (ClinicalTrials.gov ID:NCT01994382)." @default.
- W2895844167 created "2018-10-26" @default.
- W2895844167 creator A5005401772 @default.
- W2895844167 creator A5008450996 @default.
- W2895844167 creator A5021971603 @default.
- W2895844167 creator A5046480613 @default.
- W2895844167 creator A5053159281 @default.
- W2895844167 creator A5054604221 @default.
- W2895844167 creator A5056178428 @default.
- W2895844167 creator A5057376769 @default.
- W2895844167 creator A5062327095 @default.
- W2895844167 creator A5062344658 @default.
- W2895844167 creator A5063895679 @default.
- W2895844167 creator A5068917225 @default.
- W2895844167 creator A5081749777 @default.
- W2895844167 creator A5083215091 @default.
- W2895844167 date "2019-02-15" @default.
- W2895844167 modified "2023-10-18" @default.
- W2895844167 title "Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B-cell Malignancies" @default.
- W2895844167 cites W1908145345 @default.
- W2895844167 cites W1976174817 @default.
- W2895844167 cites W1977901321 @default.
- W2895844167 cites W1979816280 @default.
- W2895844167 cites W1985503770 @default.
- W2895844167 cites W1999338173 @default.
- W2895844167 cites W2001343785 @default.
- W2895844167 cites W2023400811 @default.
- W2895844167 cites W2027092131 @default.
- W2895844167 cites W2027621777 @default.
- W2895844167 cites W2028578415 @default.
- W2895844167 cites W2040604274 @default.
- W2895844167 cites W2045795253 @default.
- W2895844167 cites W2047415399 @default.
- W2895844167 cites W2058788010 @default.
- W2895844167 cites W2060829515 @default.
- W2895844167 cites W2067064694 @default.
- W2895844167 cites W2067637255 @default.
- W2895844167 cites W2070217465 @default.
- W2895844167 cites W2074369033 @default.
- W2895844167 cites W2080166898 @default.
- W2895844167 cites W2090739244 @default.
- W2895844167 cites W2091490559 @default.
- W2895844167 cites W2093766370 @default.
- W2895844167 cites W2094650342 @default.
- W2895844167 cites W2097304927 @default.
- W2895844167 cites W2097788893 @default.
- W2895844167 cites W2100162337 @default.
- W2895844167 cites W2116431837 @default.
- W2895844167 cites W2136060128 @default.
- W2895844167 cites W2154685907 @default.
- W2895844167 cites W2164323857 @default.
- W2895844167 cites W2166022914 @default.
- W2895844167 cites W2181172392 @default.
- W2895844167 cites W2212640525 @default.
- W2895844167 cites W2236553376 @default.
- W2895844167 cites W2316244721 @default.
- W2895844167 cites W2403449504 @default.
- W2895844167 cites W2528182135 @default.
- W2895844167 cites W2537764360 @default.
- W2895844167 cites W2552027239 @default.
- W2895844167 cites W2577781255 @default.
- W2895844167 doi "https://doi.org/10.1158/1078-0432.ccr-18-1047" @default.
- W2895844167 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30333224" @default.
- W2895844167 hasPublicationYear "2019" @default.
- W2895844167 type Work @default.
- W2895844167 sameAs 2895844167 @default.
- W2895844167 citedByCount "24" @default.
- W2895844167 countsByYear W28958441672019 @default.
- W2895844167 countsByYear W28958441672020 @default.
- W2895844167 countsByYear W28958441672021 @default.
- W2895844167 countsByYear W28958441672022 @default.
- W2895844167 countsByYear W28958441672023 @default.
- W2895844167 crossrefType "journal-article" @default.
- W2895844167 hasAuthorship W2895844167A5005401772 @default.
- W2895844167 hasAuthorship W2895844167A5008450996 @default.
- W2895844167 hasAuthorship W2895844167A5021971603 @default.
- W2895844167 hasAuthorship W2895844167A5046480613 @default.
- W2895844167 hasAuthorship W2895844167A5053159281 @default.
- W2895844167 hasAuthorship W2895844167A5054604221 @default.
- W2895844167 hasAuthorship W2895844167A5056178428 @default.
- W2895844167 hasAuthorship W2895844167A5057376769 @default.
- W2895844167 hasAuthorship W2895844167A5062327095 @default.
- W2895844167 hasAuthorship W2895844167A5062344658 @default.
- W2895844167 hasAuthorship W2895844167A5063895679 @default.
- W2895844167 hasAuthorship W2895844167A5068917225 @default.
- W2895844167 hasAuthorship W2895844167A5081749777 @default.
- W2895844167 hasAuthorship W2895844167A5083215091 @default.
- W2895844167 hasConcept C111113717 @default.
- W2895844167 hasConcept C112705442 @default.
- W2895844167 hasConcept C121608353 @default.
- W2895844167 hasConcept C126322002 @default.
- W2895844167 hasConcept C143998085 @default.
- W2895844167 hasConcept C159654299 @default.
- W2895844167 hasConcept C170493617 @default.
- W2895844167 hasConcept C203014093 @default.
- W2895844167 hasConcept C2776107976 @default.
- W2895844167 hasConcept C2777058707 @default.
- W2895844167 hasConcept C2777525834 @default.