gx-15-070 and Lymphoma--T-Cell

gx-15-070 has been researched along with Lymphoma--T-Cell* in 1 studies

Other Studies

1 other study(ies) available for gx-15-070 and Lymphoma--T-Cell

Article	Year
THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors. Nature communications, 2017, 01-30, Volume: 8 Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signalling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Survival; Chromatin; Cyclin-Dependent Kinase-Activating Kinase; Cyclin-Dependent Kinases; Female; Gain of Function Mutation; Gene Expression Regulation, Neoplastic; Humans; Indoles; Lymphoma, T-Cell; Male; Mice; Mice, Inbred NOD; Mice, SCID; Phenylenediamines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Pyrimidines; Pyrroles; Signal Transduction; STAT3 Transcription Factor; Transcription, Genetic; Treatment Outcome; Xenograft Model Antitumor Assays	2017

Article

Year

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors.

Nature communications, 2017, 01-30, Volume: 8

Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signalling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Survival; Chromatin; Cyclin-Dependent Kinase-Activating Kinase; Cyclin-Dependent Kinases; Female; Gain of Function Mutation; Gene Expression Regulation, Neoplastic; Humans; Indoles; Lymphoma, T-Cell; Male; Mice; Mice, Inbred NOD; Mice, SCID; Phenylenediamines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Pyrimidines; Pyrroles; Signal Transduction; STAT3 Transcription Factor; Transcription, Genetic; Treatment Outcome; Xenograft Model Antitumor Assays

2017