## The [Reproducibility Project: Cancer Biology][1] was an initiative to independently replicate selected experiments from a number of [high-profile papers][2] in the field of cancer biology. In the end 50 experiments from 23 papers were repeated. The final two outputs from the project recount in detail the challenges the project team encountered while repeating these experiments ('[Challenges for assessing replicability in preclinical cancer biology][3]'), and report the results of a meta-analysis that combined the results from all the experiments ('[Investigating the replicability of preclinical cancer biology][4]'). The project was a collaboration between the [Center for Open Science][5] and [Science Exchange][6]. ---------- Visit the [overview page][90] for additional details about the project, press & news, and how to get involved. Visit the [*eLife* collection][91] for all published papers. Visit the [OSF collection][92] for all associated digital content including the aggregate dataset. ---------- ### Replication Study Results ### Each replication was organized on the [Open Science Framework][9] (OSF). The OSF is a free service and is where all the experimental protocols, materials, data, analysis, and results were made openly available. Furthermore, the [Registered Reports][10] format was used, in which peer review of proposed experimental designs and protocols were conducted prior to data collection, in conjunction with *eLife* with the results published in a Replication Study. <br> A total of 50 experiments from 23 papers were completed. This resulted in 17 Replication Studies published at *eLife*, 1 Replication Study posted as a preprint, and the remaining completed experiments reported in a summary paper. Details for all papers below: <br> **Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology** - View the [replication results][11] published by *eLife*. - Access the OSF Project pages which contains all data, methods, and materials pertaining to the replication of this Replication Study. - [Replication of Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells][12] - [Replication of Diverse somatic mutation patterns and pathway alterations in human cancers][13] - [Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF][14] - [Replication of COT drives resistance to RAF inhibition through MAP kinase pathway reactivation][15] - [Replication of IDH mutation impairs histone demethylation and results in a block to cell differentiation][16] - View the Registered Report, which contains detailed, peer-reviewed, protocols for this replication. - [Registered report: Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells][17] - [Registered report: Diverse somatic mutation patterns and pathway alterations in human cancers][18] - [Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF][19] - [Registered report: COT drives resistance to RAF inhibition through MAP kinase pathway reactivation][20] - [Registered report: IDH mutation impairs histone demethylation and results in a block to cell differentiation][21] **Replication Study: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth** - View the [Replication Study results][22] posted as a preprint on [bioRxiv][23]. - Access the [OSF Project page][24] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][25], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs** - View the [Replication Study results][26] published by *eLife*. - Access the [OSF Project page][27] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][28], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology** - View the [Replication Study results][29] published by *eLife*. - Access the [OSF Project page][30] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][31], which contains detailed, peer-reviewed, protocols for this replication. - View the [Insight article][32] published alongside this Replication Study. **Replication Study: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis** - View the [Replication Study results][33] published by *eLife*. - Access the [OSF Project page][34] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][35], which contains detailed, peer-reviewed, protocols for this replication. - View the [Insight article][36] published alongside this Replication Study. **Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment** - View the [Replication Study results][37] published by *eLife*. - Access the [OSF Project page][38] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][39], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44** - View the [Replication Study results][40] published by *eLife*. - Access the [OSF Project page][41] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][42], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET** - View the [Replication Study results][43] published by *eLife*. - Access the [OSF Project page][44] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][45], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Intestinal inflammation targets cancer-inducing activity of the microbiota** - View the [Replication Study results][46] published by *eLife*. - Access the [OSF Project page][47] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][48], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: _Fusobacterium nucleatum_ infection is prevalent in human colorectal carcinoma** - View the [Replication Study results][49] published by *eLife*. - Access the [OSF Project page][50] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][51], which contains detailed, peer-reviewed, protocols for this replication. - View the [Insight article][52] published alongside this Replication Study. **Replication Study: Transcriptional amplification in tumor cells with elevated c-Myc** - View the [Replication Study results][53] published by *eLife*. - Access the [OSF Project page][54] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][55], which contains detailed, peer-reviewed, protocols for this replication. - View the [Insight article][56] published alongside this Replication Study. **Replication Study: Systematic identification of genomic markers of drug sensitivity in cancer cells** - View the [Replication Study results][57] published by *eLife*. - Access the [OSF Project page][58] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][59], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia** - View the [Replication Study results][60] published by *eLife*. - Access the [OSF Project page][61] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][62], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate** - View the [Replication Study results][63] published by *eLife*. - Access the [OSF Project page][64] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][65], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Coadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs** - View the [Replication Study results][66] published in *eLife*. - Access the [OSF Project page][67] to view all data, methods, and materials pertaining to this Replication Study. - View the [Registered Report][68], which contains detailed, peer-reviewed, protocols for this Replication Study. **Replication Study: BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc** - View the [Replication Study results][69] published in *eLife*. - Access the [OSF Project page][70] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][71], which contains detailed, peer-reviewed, protocols for this Replication Study. - View the [Insight article][72] published alongside this Replication Study. **Replication Study: Discovery and Preclinical Validation of Drug Indications using Compendia of Public Gene Expression Data** - View the [Replication Study results][73] published in *eLife*. - Access the [OSF Project page][74] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][75], which contains detailed, peer-reviewed, protocols for this Replication Study. - View the [Insight article][76] published alongside this Replication Study. **Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors** - View the [Replication Study results][77] published in *eLife*. - Access the [OSF Project page][78], which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][79], which contains detailed, peer-reviewed, protocols for this replication. **Replication Study: Melanoma genome sequencing reveals frequent PREX2 mutations** - View the [Replication Study results][80] published by *eLife*. - Access the [OSF Project page][81] which contains all data, methods, and materials pertaining to the replication of this Replication Study. - View the [Registered Report][82], which contains detailed, peer-reviewed, protocols for this replication. - View the [Insight article][83] published alongside this Replication Study. ---------- ### Additional articles and commentary published on this project: ## For more information read the [Introductory commentary][84] published by *eLife* that introduces and summarizes the project and the corresponding [editorial][85] as well as the [Replication commentary][86] and the corresponding [editorial][87] from *eLife* from the first published Replication Studies. The final eLife [editorial][88] and an [independent commentary][89] compliment the final summary papers. ----------- ### What were the aims of the project? Through independent direct replication studies, the project aimed to identify best practices that maximize reproducibility and facilitate an accurate accumulation of knowledge, enabling potentially impactful novel findings to be effectively built upon by the scientific community. Additionally we expected to learn about: - The overall rate of reproducibility in a sample of the published cancer biology literature. - Obstacles that arise in conducting direct replications of original studies. - The feasibility and practical challenges of getting proper materials, methods, and instrumentation for a replication. - Predictors of replication success. ---------- Questions or interest in the project can be directed to <a href="mailto:contact+rpcb@cos.io">contact+rpcb@cos.io</a>. ---------- [1]: https://cos.io/rpcb [2]: https://osf.io/e81xl/wiki/studies [3]: https://elifesciences.org/articles/67995 [4]: https://elifesciences.org/articles/71601 [5]: http://centerforopenscience.org/ [6]: https://www.scienceexchange.com/ [7]: http://elifesciences.org/collections/reproducibility-project-cancer-biology [8]: https://elifesciences.org [9]: https://osf.io [10]: https://osf.io/8mpji/wiki/home/ [11]: https://elifesciences.org/articles/73430 [12]: https://osf.io/mpyvx/wiki/home [13]: https://osf.io/jpeqg/wiki/home [14]: https://osf.io/b1aw6/wiki/home [15]: https://osf.io/lmhjg/wiki/home [16]: https://osf.io/vfsbo/ [17]: https://elifesciences.org/articles/04363 [18]: https://elifesciences.org/articles/11566 [19]: https://elifesciences.org/articles/11999 [20]: https://elifesciences.org/articles/11414 [21]: https://elifesciences.org/articles/10860 [22]: https://doi.org/10.1101/2021.11.30.470372 [23]: https://www.biorxiv.org/ [24]: https://osf.io/0hezb/ [25]: https://elifesciences.org/articles/09976 [26]: https://elifesciences.org/articles/56651 [27]: https://osf.io/oblj1/wiki/home [28]: https://elifesciences.org/articles/12470 [29]: https://elifesciences.org/articles/51019 [30]: https://osf.io/yyqas/wiki/home/ [31]: https://elifesciences.org/articles/08245 [32]: https://elifesciences.org/articles/56397 [33]: https://elifesciences.org/articles/45120 [34]: https://osf.io/7yqmp/wiki/home/ [35]: https://elifesciences.org/articles/04796 [36]: https://elifesciences.org/articles/53511 [37]: https://doi.org/10.7554/eLife.45426 [38]: https://osf.io/pgjhx/wiki/home/ [39]: https://elifesciences.org/articles/07301 [40]: https://elifesciences.org/articles/43511 [41]: https://osf.io/gb7sr/wiki/home/ [42]: https://elifesciences.org/articles/06434 [43]:https://elifesciences.org/articles/39944 [44]:https://osf.io/ewqzf/wiki/home [45]:https://elifesciences.org/articles/07383 [46]: https://elifesciences.org/articles/34364 [47]: https://osf.io/y4tvd/wiki/home/ [48]: https://elifesciences.org/articles/04186 [49]: https://elifesciences.org/articles/25801 [50]: https://osf.io/v4se2/wiki/home/ [51]: https://elifesciences.org/articles/10012 [52]: https://elifesciences.org/articles/28434 [53]: https://doi.org/10.7554/eLife.30274 [54]: https://osf.io/mokeb/wiki/home/ [55]: https://elifesciences.org/articles/04024 [56]: https://elifesciences.org/articles/32010 [57]: https://doi.org/10.7554/eLife.29747 [58]: https://osf.io/nbryi/wiki/home/ [59]: https://elifesciences.org/articles/13620 [60]: https://elifesciences.org/articles/25306 [61]: https://osf.io/hcqqy/wiki/home/ [62]: https://elifesciences.org/articles/08997 [63]: https://elifesciences.org/articles/26030 [64]: https://osf.io/8l4ea/wiki/home/ [65]: https://elifesciences.org/articles/12626v1 [66]: http://dx.doi.org/10.7554/eLife.17584 [67]: https://osf.io/xu1g2/wiki/home/ [68]: https://elifesciences.org/content/4/e06959 [69]: http://dx.doi.org/10.7554/eLife.21253 [70]: https://osf.io/7zqxp/wiki/home/ [71]: https://elifesciences.org/content/4/e07072 [72]: http://dx.doi.org/10.7554/eLife.22915 [73]: http://dx.doi.org/10.7554/eLife.17044 [74]: https://osf.io/hxrmm/wiki/home/ [75]: https://elifesciences.org/content/4/e06847 [76]: http://dx.doi.org/10.7554/eLife.22661 [77]: http://dx.doi.org/10.7554/eLife.18173 [78]: https://osf.io/9pbos/wiki/home/ [79]: https://elifesciences.org/content/4/e04586 [80]: http://dx.doi.org/10.7554/eLife.21634 [81]: https://osf.io/jvpnw/wiki/home/ [82]: https://elifesciences.org/content/3/e04180 [83]: http://dx.doi.org/10.7554/eLife.22662 [84]: https://elifesciences.org/content/3/e04333 [85]: https://elifesciences.org/content/3/e03981 [86]: http://dx.doi.org/10.7554/eLife.23383 [87]: http://dx.doi.org/10.7554/eLife.23693 [88]: https://elifesciences.org/articles/75830 [89]: https://elifesciences.org/articles/67527 [90]: https://www.cos.io/rpcb [91]: https://elifesciences.org/collections/9b1e83d1/reproducibility-project-cancer-biology [92]: https://osf.io/collections/rpcb/