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Ref Type Journal Article
PMID (32269732)
Authors Yang J, Hu S, Shangguan J, Eresen A, Li Y, Ma Q, Yaghmai V, Benson Iii AB, Zhang Z
Title Dinaciclib prolongs survival in the LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) transgenic murine models of pancreatic ductal adenocarcinoma.
Journal Vol Issue Date Pages Journal Short Title
American journal of translational research 12 3 2020 1031-1043 Am J Transl Res
URL
Abstract Text Dinaciclib is a small molecule cyclin-dependent kinase inhibitor with the potential to treat multiple cancers. To better understand its cytotoxic action in pancreatic ductal adenocarcinoma (PDAC), we evaluated dinaciclib therapeutic effects in the transgenic mouse model (LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre mice; KPC mice). Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Dinaciclib therapy significantly delayed tumor progression (P < 0.001) and prolonged survival (P = 0.007) in KPC mice. In vitro assays showed that dinaciclib exerted antiproliferative effects on PDAC cells by increasing surface calreticulin expression and release of ATP. Dinaciclib treatment inhibited proliferation and induced apoptosis in KPC tumor as assessed by Ki67 and cleaved caspase 3, respectively. Particularly, the tumor infiltrating CD8+ T cells were increased after dinaciclib treatment in KPC mice. Additionally, the mean apparent diffusion coefficient values of KPC tumor calculated from diffusion weighted MR images were significantly lower after dinaciclib treatment (P = 0.033). These finding suggest that dinaciclib as a single agent can inhibit tumor growth and improve the overall survival in KPC mice.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Dinaciclib Dinaciclib 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Dinaciclib SCH727965|MK-7965|SCH-727965 CDK1 Inhibitor 13 CDK2 Inhibitor 30 CDK5 Inhibitor 8 CDK9 Inhibitor 21 Dinaciclib (SCH 727965) inhibits cyclin dependent kinases CDK1, CDK2, CDK5, CDK9, and CDK12, which prevents phosphorylation of downstream targets and may promote cell cycle arrest and apoptosis in cancer cells (PMID: 24900195, PMID: 24004674, PMID: 27880910, PMID: 32269732).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References