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## Registered report: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth <br> **Abstract:** The [Reproducibility Project: Cancer Biology][1] seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of [citations and Altmetric scores][2] ([Errington et al., 2014][3]). This Registered Report describes the proposed replication plan of key experiments from "RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth" by Hatzivassiliou and colleagues, published in *Nature* in 2010 ([Hatzivassiliou et al., 2010][4]). Hatzivassiliou and colleagues examined the paradoxical response of RAF-WT tumors to treatment with RAF inhibitors. The key experiments being replicated include Figure 1A, in which the original authors demonstrated that treatment of a subset of BRAF<sup>WT</sup> tumor cell lines with RAF small molecule inhibitors resulted in an increase in cell viability, Figure 2B, which reported that RAF inhibitor activation of the MAPK pathway was dependent on CRAF but not BRAF, and Figure 4A, where the dimerization of BRAF and CRAF was modulated by the RAF inhibitor PLX4720, but not GDC-0879. The Reproducibility Project: Cancer Biology is a collaboration between the [Center for Open Science][5] and [Science Exchange][6], and the results of the replications will be published by [*eLife*][7]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 8: Hatzivassiliou et al., 2010 (*Nature*). The Registered Report can be found [here][8]. **Registered Report Initial Draft**: - This document represents the first draft of the selected experimental protocols. It contains the information that the Core team, with help from scientist volunteers, was able to glean from the original publication and its supplemental materials before the original authors were contacted for their input. - [Study 8 Registered Report Initial Draft][9] **Power Calculations**: - These documents contain details about how power calculations were performed, and include spreadsheets documenting statistical tests as well as any PRISM files, R scripts or additional materials used. - [Study 8 Power Calculations][10] - [Figure 2B Data Estimates.csv][11] - [Study 8 Protocol 2 Figure 2B ANOVA.R][12] - [Study 8 Protocol 3 Figure 4A 2-way ANOVA.R][13] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://osf.io/e81xl/wiki/studies/ [3]: https://elifesciences.org/articles/04333 [4]: https://doi.org/10.1038/nature08833 [5]: http://centerforopenscience.org/ [6]: https://www.scienceexchange.com/ [7]: https://elifesciences.org/ [8]: https://elifesciences.org/articles/09976 [9]: https://osf.io/4m3d6/ [10]: https://osf.io/rp6sq/ [11]: https://osf.io/mn56f/ [12]: https://osf.io/uf49v/ [13]: https://osf.io/bmz3x/
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