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BioAssay: AID 2721

Summary of Broad Institute MLPCN Breast Cancer Stem Cell Toxicity Project

Cancer stem cells (CSCs), which drive tumor growth, are known to be resistant to standard chemotherapy and radiation treatment. This raises a very significant unmet need to find therapies that can target CSCs within tumors, since these cells are responsible for recurrence - the primary cause of patient mortality. In principle, it would be desirable to apply high-throughput screening (HTS) more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Probe(3)
 
 
Active(3)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Probe(4)
 
 
Active(4)
 
 
 Related BioAssays
 Related BioAssays
AID: 2721
Data Source: Broad Institute (2058-01_INHIBITORS_PROJECT)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-03-30
Modify Date: 2012-01-24

Data Table ( Complete ):           Active    All
BioActive Compounds: Chemical Probe: 3    Active: 3
Depositor Specified Assays
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AIDNameTypeComment
2717Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cellsscreening300718 hts compounds at singlepoint in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity
449748Luminescence Cell-Based Dose Retest to Confirm Inhibitors of Cancer Stem Cellsconfirmatory2243 cherrypick compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 1
463074Dose Response HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFPconfirmatory2243 cherrypick compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 1
493176Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set3confirmatory19 drypowder compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 3
493196HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set3confirmatory19 drypowder compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 3
493226Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory65 drypowder compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 2
504325HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory65 drypowder compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 2
504449Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set4confirmatory76 drypowder compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 4
504450HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set4confirmatory76 drypowder compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 4
504535Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set5confirmatory45 drypowder compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 5
504533HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set5confirmatory45 drypowder compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 5
504623Orthogonal assay for the inhibition of tumorsphere formation Measured in Cell-Based System Using Imaging - 2058-03_Inhibitor_SinglePoint_DryPowder_Activityconfirmatory16 drypowder compounds at singlepoint in Tumorsphere_SUM159 measuring activity
504667Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set6confirmatory64 drypowder compounds at dose in Primary HTS shECAD_HMLE CellTiterGlo viability measuring activity set 6
504666HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set6confirmatory64 drypowder compounds at dose in Secondary HMLE_sh_eGFP measuring activity set 6
504788Luminescence Cell-Based Primary HTS to Identify Inhibitors of Cancer Stem Cells Measured in Cell-Based System Using Plate Reader - 2058-01_Inhibitor_Dose_DryPowder_Activity_Set7confirmatory
504789HTS Screen to Identify Cytotoxic Compounds of HMLE_sh_eGFP Measured in Cell-Based System Using Plate Reader - 2058-02_Inhibitor_Dose_DryPowder_Activity_Set7confirmatory
504859Orthogonal assay for the inhibition of tumorsphere formation Measured in Cell-Based System Using Imaging - 2058-03_Inhibitor_SinglePoint_DryPowder_Activity_Set2other
588702Luminescence-based toxicity of Human Mammary Epithelial (HMLE) cells_2058-08_Inhibitor_Dose_DryPowder_Activityconfirmatory
588703Luminescence-based toxicity of HMLE_shTWIST Breast Cancer Stem Cell-like cells_2058-07_Inhibitor_Dose_DryPowder_Activityconfirmatory
588704Luminescence-based toxicity of HMLE_shECAD Breast Cancer Stem Cell-like cells_2058-06_Inhibitor_Dose_DryPowder_Activityconfirmatory
588705Luminescence-based toxicity of MDA231 Breast Cancer cells_2058-09_Inhibitor_Dose_DryPowder_Activityconfirmatory
588840uminescence-based toxicity of MDA231 Breast Cancer cells Measured in Cell-Based System Using Plate Reader - 2058-09_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
588844Luminescence-based toxicity of HMLE_shECAD Breast Cancer Stem Cell-like cells Measured in Cell-Based System Using Plate Reader - 2058-06_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
588845Luminescence-based toxicity of HMLE_shTWIST Breast Cancer Stem Cell-like cells Measured in Cell-Based System Using Plate Reader - 2058-07_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
588846Luminescence-based toxicity of Human Mammary Epithelial (HMLE) cells Measured in Cell-Based System Using Plate Reader - 2058-08_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
Description:
Keywords: Breast Cancer Stem Cells

Primary Collaborators:
Pyush Gupta, Broad Institute, Cambridge, MA, piyush@broadinstitute.org, 617-714-7498
Eric Lander, Broad Institute, Cambridge, MA, lander@broadinstitute.org

Biological Relevance:
Cancer stem cells (CSCs), which drive tumor growth, are known to be resistant to standard chemotherapy and radiation treatment. This raises a very significant unmet need to find therapies that can target CSCs within tumors, since these cells are responsible for recurrence - the primary cause of patient mortality. In principle, it would be desirable to apply high-throughput screening (HTS) technologies to facilitate the identification of chemical compounds that specifically target CSCs. However, since CSCs generally comprise only small minorities within cancer cell populations, standard high-throughput cell viability assays applied to bulk populations of cancer cells cannot identify agents with CSC-specific toxicity. Accordingly, screening for agents that preferentially kill CSCs depends at present on the ability to obtain and stably propagate highly pure CSC populations in vitro. Since CSCs cannot currently be stably propagated in culture it has not been possible to leverage HTS to identify CSC-targeting compounds.

We have recently discovered a novel HTS assay to identify selective inhibitors of cancer stem cells. This approach is to use stable sibling cell lines that are induced into epithelial-to-mesenchymal transdifferentiation (EMT) as a method to stably propagate CSC-enriched populations. The availability of isogenic control cell lines for the secondary validation assay of the proposed screen, which is absent in most screens, minimizes the probability of finding spurious compound hits that are not selective for CSCs but rather target genetic differences between screened cell lines.

Project Goal:
The objective of the experiments in this proposal is to identify chemical compounds that can selectively kill breast cancer stem cells (CSCs). The HMLE cell line suppressing E-Cadherin expression (HMLE_shECad) is a stable cell line that has been induced into epithelial-to-mesenchymal transdifferentiation (EMT). The chemical compounds that selectively kill CSCs would be promising new drug candidates for anti-cancer therapy and would also serve as useful probes to study CSC biology, which are currently lacking.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ML_NUMML number assigned to the compound.String
Additional Information
Grant Number: 1 R03 MH089663-01

Data Table (Concise)
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