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Published on: May 15, 2019
Registered report: BET bromodomain inhibition as a therapeutic strategy to target c-Myc
Irawati Kandela1, Hyun Yong Jin2, Katherine Owen3
1Developmental Therapeutics Core, Northwestern University, Evanston, Illinois.
Abstract:
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from 'BET bromodomain inhibition as a therapeutic strategy to target c-Myc' by Delmore and colleagues, published in Cell in 2011 (Delmore et al., 2011). The key experiments that will be replicated are those reported in Figures 3B and 7C-E. Delmore and colleagues demonstrated that treatment with JQ1, a small molecular inhibitor targeting BET bromodomains, resulted in the transcriptional down-regulation of the c-Myc oncogene in vitro (Figure 3B; Delmore et al., 2011). To assess the therapeutic efficacy of JQ1 in vivo, mice bearing multiple myeloma (MM) lesions were treated with JQ1 before evaluation for tumor burden and overall survival. JQ1 treatment significantly reduced disease burden and increased survival time (Figure 7C-E; Delmore et al., 2011). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.
Insights
This study replicates cancer research on BET bromodomain inhibitors. JQ1 effectively reduced c-Myc oncogene expression and improved survival in multiple myeloma mouse models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Reproducibility in scientific research is a growing concern.
- The Reproducibility Project: Cancer Biology aims to replicate key findings from high-impact cancer studies.
- This report details the replication plan for experiments from Delmore et al., 2011, published in Cell.
Purpose of the Study:
- To replicate in vitro and in vivo experiments on BET bromodomain inhibition targeting the c-Myc oncogene.
- To validate the therapeutic potential of JQ1 in cancer models.
- To contribute to the growing body of evidence on the reproducibility of cancer biology research.
Main Methods:
- Replication of experiments reported in Figure 3B (in vitro) and Figures 7C-E (in vivo) from Delmore et al., 2011.
- Utilizing JQ1, a small molecule inhibitor of BET bromodomains.
- Assessing transcriptional down-regulation of c-Myc and evaluating tumor burden and survival in a multiple myeloma mouse model.
Main Results:
- Delmore et al. (2011) demonstrated that JQ1 down-regulates c-Myc expression in vitro.
- Delmore et al. (2011) showed that JQ1 treatment reduced tumor burden and increased survival in mice with multiple myeloma.
- This registered report outlines the planned replication of these specific findings.
Conclusions:
- The replication of these key experiments will provide valuable data on the robustness of findings regarding BET bromodomain inhibitors in cancer biology.
- Successful replication would support JQ1 as a potential therapeutic strategy for cancers involving c-Myc.
- The results will be published in eLife, contributing to open science and research reproducibility.
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