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Scientists Replicate Studies for the Reproducibility Project: Cancer Biology

Rigor and reproducibility are essential to the ability of scientific discoveries to advance scientific knowledge and to enable its translation into therapeutics and diagnostics in the clinic.  Senior staff researchers of the Center for Developmental Therapeutics (CDT), Irawati Kandela, Fraser Aird, and Christine Mantis, are playing a significant role inThe Reproducibility Project: Cancer Biology through their efforts to reproduce the findings of three seminal studies in the field of cancer biology.  These replication studies were the among the first five associated with the Reproducibility to be published on January 19th in eLife.  Commentaries on their findings were published in major scientific journals, including Science and Nature and earned a featured place in NPR’s Science Friday broadcast and an article in the Washington Post.

The studies replicated by the Center for Developmental Therapeutics were previously published as: “BET bromodomain inhibition as a therapeutic strategy to target c-Myc”, Cell 2011,146: 904-917;  “Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs”, Science 2010, 328:1031-1035; and “Discovery and preclinical validation of drug indications using compendia of public gene expression data”, Science Translational Medicine 2011, 3:96ra77.

The Reproducibility Project: Cancer Biology is a collaboration between Science Exchange and the Center for Open Science, and is independently replicating a subset of experimental results from a number of high-profile papers in the field of cancer biology studies published between 2010-2012 using the Science Exchange network of expert scientific labs.

CDT was selected to receive funding from the Reproducibility Project to replicate these studies.  They were required to first develop a Registered Report detailing the proposed experimental designs and protocols for the replications, which was then peer reviewed and published prior to replicating the original studies. Once the report was approved they embarked on the Replication Study experiments using the same protocols and materials as the original published study.  Once the replication studies were completed they were submitted for final review before publication.

Despite the use of exacting study design CDT scientists were unable to match the results of the original studies.  Their studies failed to demonstrate significant efficacy of the compounds the new therapeutics tested in the original studies for treatment of cancer in animal models.  Copies of the registered reports and the CDT replication studies can be found at https://elifesciences.org/collections/reproducibility-project-cancer-biology.

For the CDT scientists, this experience highlighted the importance of providing detailed information about the methods, protocols and reagents used when publishing scientific data.  They found that replication of the original studies was confounded by lack of detailed information and information gaps in the original publications that generated important questions requiring clarification from the original study authors, which were met with varying degrees of co-operation.

The Center for Developmental Therapeutics (CDT) was established to rapidly and efficiently advance novel therapeutic interventions from basic research to the clinic. The CDT is one of the first academic-based drug development centers that bridges all aspects of translational research in a single entity including early drug discovery, mechanistic research, pre-clinical development and translation into the clinic.

http://clp.northwestern.edu/news/scientists-replicate-studies-reproducibility-project-cancer-biology

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