## Registered report: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion <br> **Abstract:** The [Reproducibility Project: Cancer Biology][1] seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from ‘Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion’ by Straussman and colleagues, published in *Nature* in 2012 ([Straussman et al., 2012][2]). The key experiments being replicated in this study are from Figure 2A, C, and D (and Supplemental Figure 11) and Figure 4C (and Supplemental Figure 19) ([Straussman et al., 2012][3]). Figure 2 demonstrates resistance to drug sensitivity conferred by co-culture with some stromal cell lines and identifies the secreted factor responsible as HGF. In Figure 4, Straussman and colleagues show that blocking the HGF receptor MET abrogates HGF’s rescue of drug sensitivity. The Reproducibility Project: Cancer Biology is a collaboration between the [Center for Open Science][4] and [Science Exchange][5], and the results of the replications will be published by [*eLife*][6]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 40: Straussman et al. 2012, Nature. The Registered Report can be found [here][7]. ---------- **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 40 Registered Report initial draft][8] **Data Estimation**: - When original data was unable to be obtained, or original qualitative data was quantified (for example, Western blots), the estimated data is contained here. Examples include densitometric quantification of Western blot bands, or estimations of means and variances from published graphs. - [Study 40 Protocol 6 estimates.xlsx][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 40 Power Calculations][10] - [Study 40 Protocol 3 1-way Anova.pzfx][11] - [Study 40 Protocol 4 1-way and 2-way ANOVAs.pzfx][12] - [Study 40 Protocol 5 3-way ANOVA.R][13] - [Study 40 Protocol 5 2-way Anovas.pzfx][14] - [Study 40 Protocol 6 3-way ANOVA.R][15] - [Study 40 Protocol 6 2-way ANOVAs.pzfx][16] ---------- **Meta-analysis of Straussman et al., 2012 and Lezcano et al., 2014:** - A random-effects model was used to combine the effect sizes calculated from the reported data in Supplemental Table 7 and presented in Figure 3C from [Straussman et al., 2012][17] and the reported data in Table 1 and presented in Figure 3C from [Lezcano et al., 2014][18]. These experiments compared clinical outcomes in patients that were negative or positive for HGF in pre-treatment peri-tumoral stroma as determined by immunohistochemistry. These documents contain details about how the meta-analysis was performed and a forest plot of the individual study effect sizes and the combined effect size with 95% confidence intervals. - [Forest plot][19] - [Summary of individual study effect sizes and meta-analysis][20] - [Analysis script of individual study effect sizes and meta-analysis][21] - [Data file for importing into R for analysis][22] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://doi.org/10.1038/nature11183 [3]: https://doi.org/10.1038/nature11183 [4]: http://centerforopenscience.org/ [5]: https://www.scienceexchange.com/ [6]: https://elifesciences.org/ [7]: http://elifesciences.org/content/3/e04034 [8]: https://osf.io/eh4qy/ [9]: https://osf.io/pixgv/ [10]: https://osf.io/cjxs6/ [11]: https://osf.io/xt68b/ [12]: https://osf.io/75h6e/ [13]: https://osf.io/ipfen/ [14]: https://osf.io/pgr7c/ [15]: https://osf.io/s7gmv/ [16]: https://osf.io/bi4r7/ [17]: http://www.nature.com/nature/journal/v487/n7408/full/nature11183.html [18]: http://www.nature.com/modpathol/journal/v27/n9/full/modpathol2013226a.html [19]: https://osf.io/g9p4t/ [20]: https://osf.io/s82pz/ [21]: https://osf.io/tfz3b/ [22]: https://osf.io/ua5nw/