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CB-839 + Capecitabine in Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer

ABSTRACT: This study has two portions. The main goal of the Phase I portion of this research study is to see what doses of CB-839 and capecitabine can safely be given to patients without having too many side effects. Other purposes of this research study will be to determine what side effects are seen with this combination of medicines. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment.

DISEASE(S): Solid Tumor,Colon Cancer,Colorectal Cancer,Colorectal Neoplasms,Rectal Cancer

PROVIDER: 2221973 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Yttrium-90 Radioembolization + Nivolumab for Liver + Extra-hepatic Metastases From Colorectal Cancer

Project description:This study has two portions. The main goal of the Phase Ib portion of this research study is to see at what time Yttrium-90 (Y-90) radioembolization therapy and nivolumab can safely be given to patients without having too many side effects. Other purposes of this research study will be to study any tumor responses. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment. The study team will pick the part of the study each subject participates in. Y-90 radioembolization therapy is minimally invasive procedure that combines two types of therapy (embolization which blocks certain blood vessels, and radiation therapy, which kills cancer cells) to treat cancer tumors in the liver. This works with tiny glass or resin beads filled with the radioactive isotope yttrium-90 (Y-90). They are placed inside the blood vessels that feed the tumor in the liver. This blocks the supply of blood to the cancer cells and delivers a high dose of radiation to the tumor while sparing normal tissue. Nivolumab is an FDA approved medicine that is used for the treatment of different types of cancers and metastases (second growths from cancer).

| 2256236 | ecrin-mdr-crc

Burkholderia pseudomallei CB strain:CB

Project description:Burkholderia pseudomallei CB strain:CB Genome sequencing and assembly

| PRJNA188497 | ENA

Clostridium botulinum strain:CB-27 | isolate:CB-27

Project description:Clostridium botulinum strain:CB-27 | isolate:CB-27 Genome sequencing

| PRJNA611674 | ENA

beta proteobacterium CB

Project description:Beta proteobacterium CB Genome

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Molecular Signatures of CB-6644 inhibition of the RUVBL1/2 complex in Multiple Myeloma [RNA-seq]

Project description:Multiple Myeloma is the second most hematological cancer. RUVBL1 and RUVBL2 forms a subcomplex of many chromatin remodeling complexes implicated in cancer progress. As an inhibitor specific to the RUVBL1/2 complex, CB-6644 exhibits remarkable anti-tumor activity in xenograft models of Burkitt’s lymphoma and multiple myeloma (MM). In this work, we defined transcriptional signatures corresponding to CB-6644 treatment in MM cells and determined underlying epigenetic changes in terms of chromatin accessibility.CB-6644 upregulated biological processes related to interferon response and downregulated those linked to cell proliferation in MM cells. Transcriptional regulator inference identified ATF4/CEBP and E2Fs as regulators for downregulated genes and MED1 and MYC as regulators for upregulated genes. CB-6644-induced changes in chromatin accessibility occurred mostly in non-promoter regions. Footprinting analysis identified transcription factors implied in modulating chromatin accessibility in response to CB-6644 treatment, including ATF4/CEBP and IRF4. Lastly, integrative analysis of transcription responses to various chemical compounds of the molecular signature genes from public gene expression data identified CB-5083, a p97 inhibitor, as a synergistic candidate with CB66-44 in MM cells, but experimental validation refuted this hypothesis.

2024-08-19 | GSE271840 | GEO

Molecular Signatures of CB-6644 inhibition of the RUVBL1/2 complex in Multiple Myeloma [ATAC-seq]

2024-08-19 | GSE271838 | GEO

Gene expression profile of multiple myeloma cell lines treated with CB-5083

Project description:The goal was to determine the gene expression differences between CB-5083 and Bortezomib treated multiple myeloma cell lines Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis. CB-5083 decreases viability in MM cell lines and patient derived MM cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant MM models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with MM standard of care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several MM disease models and provide the rationale for clinical evaluation as monotherapy and in combination in MM.

2017-10-26 | GSE101923 | GEO

Development of gene expression signatures for cord blood (CB)-derived MDSCs

Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish CB-MDSCs treated with or without combined cytokines, and CB-MDSCs cultured in complete or glucose-deprived medium.

2016-12-19 | GSE92367 | GEO

HCT116 cells treated with the p97 inhibitior CB-5083

Project description:The goal of this study was to analyze differential gene expression 8 hr after treatment of CB-5083, a small molecule inhibitor of p97 (VCP), in HCT116 cells grown in culture. DMSO treated cells were compared to cells treated with 1uM CB-5083 after 8 hr.

2015-11-09 | E-GEOD-73588 | biostudies-arrayexpress

Gene expression from induced CB-derived neurons at different time of differentiation

Project description:Gene expression from cord blood stem cells and respective derived neuronal cells at different times point of differentiation:CD133+ cells; Keywords: Expression Profiling by array We analyzed 3 arrays from each condition and 2 arrays for the positive controls:CB CD133+ untreated,CB-iNCs after SOX2 and cMYC overexpression, CB-neurons after differentiation (6 weeks), HUES6-NPCs control, HUES6-neurons control

2012-06-04 | E-GEOD-38431 | biostudies-arrayexpress

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