## Registered report: A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations <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 substantial 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 experiments from “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations” by Sharma and colleagues, published in *Cell* in 2010 ([Sharma et al., 2010][4]). Sharma and colleagues demonstrated that prolonged exposure of cancer cells to TKIs give rise to small populations of “drug tolerant persisters” (DTPs) (Figure 1B-C) that were reversed during subsequent maintenance under drug-free conditions (Figures 1E, 2B and 2E). DTPs exhibited reduced histone acetylation and sensitivity to HDAC inhibitors (HDIs) (Figure 4A-B). Drug sensitivity was restored with co-treatment of either HDIs or an IGF-1R inhibitor, in combination with TKIs (Figure 5A-B). Inhibition of IGF-1R activation also led to decreased KDM5A expression and restoration of H3K4 methylation, suggesting a direct link between the IGF-1R signaling pathway and KDM5A function (Figure 7A, 7C, and 7I). 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 in [*eLife*][7]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 2: Sharma et al. 2010, *Cell*. 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 2 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 2 Power calculations][10] - [Protocol 2 data estimation summary][11] - [Study 2 graph data estimation][12] - [Study 2 Protocol 4 2-way ANOVA.R][13] - [Study 2 Protocol 5 Figure 1B Cochran-Mantel-Haenszel test.R][14] - [Study 2 Protocol 5 Figure 4B 2-way ANOVA.R][15] - [Study 2 Protocol 7 2-way ANOVA.R][16] - [Study 2 Protocol 8 2-way ANOVA.R][17] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://osf.io/e81xl/wiki/studies/ [3]: https://doi.org/10.7554/eLife.04333 [4]: https://doi.org/10.1016/j.cell.2010.02.027 [5]: http://centerforopenscience.org/ [6]: https://www.scienceexchange.com/ [7]: https://elifesciences.org/ [8]: https://elifesciences.org/articles/09462 [9]: https://osf.io/whkus/ [10]: https://osf.io/ms6f3/ [11]: https://osf.io/cbewt/ [12]: https://osf.io/fpntx/ [13]: https://osf.io/am7c6/ [14]: https://osf.io/8khgd/ [15]: https://osf.io/e92ux/ [16]: https://osf.io/uqfak/ [17]: https://osf.io/cq46h/