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GSE15396
Homo sapiens
147 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Publication Title
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Publication Title
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses, and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis.
Publication Title
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genes responses in A549 and H460 cells after GSI (RO4929097-001-003 , 2 uM) treatment.
Publication Title
Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 219 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Race, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Disease, Cell line, Race, Time
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Specimen part, Cell line, Race
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
Publication Title
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sample Metadata Fields
Sex, Specimen part, Cell line, Race
View Samples