title: Registered report: BET bromodomain inhibition as a therapeutic strategy to target c-Myc.
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.
authors.affiliation: Developmental Therapeutics Core, Northwestern University, Evanston, Illinois.
authors.forename: Irawati
authors.initials: I
authors.lastname: Kandela
authors.affiliation: The Scripps Research Institute, La Jolla, California.
authors.forename: Hyun Yong
authors.initials: HY
authors.lastname: Jin
authors.affiliation: University of Virginia, Charlottesville, Virgina.
authors.forename: Katherine
authors.initials: K
authors.lastname: Owen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D001381:Azepines / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000378:metabolism / Q000627:therapeutic use
chemical_list: C561695:(+)-JQ1 compound; D000970:Antineoplastic Agents; D001381:Azepines; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014230:Triazoles
keywords: Reproducibility Project: Cancer Biology; bromodomain inhibitor; human; human biology; medicine; methodology; mouse; myeloma; targeted therapy