2024-08-27 パデュー大学
<関連情報>
- https://www.purdue.edu/research/features/stories/purdue-invented-tool-reveals-untapped-efficacy-of-cancer-drug-leveling-up-cancer-fight/
- https://www.nature.com/articles/s41467-024-51859-9
パスウェイ・アンサンブル・ツールとベンチマークを用いて、癌経路と治療薬を偏りなく発見 Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark
Luopin Wang,Aryamav Pattnaik,Subhransu Sekhar Sahoo,Ella G. Stone,Yuxin Zhuang,Annaleigh Benton,Md Tajmul,Srishti Chakravorty,Deepika Dhawan,My An Nguyen,Isabella Sirit,Kyle Mundy,Christopher J. Ricketts,Marco Hadisurya,Garima Baral,Samantha L. Tinsley,Nicole L. Anderson,Smriti Hoda,Scott D. Briggs,Hristos Z. Kaimakliotis,Brittany L. Allen-Petersen,W. Andy Tao,W. Marston Linehan,Deborah W. Knapp,… Majid Kazemian
Nature Communications Published:24 August 2024
DOI:https://doi.org/10.1038/s41467-024-51859-9
Abstract
Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create “Benchmark” to critically evaluate existing tools and find that most function sub-optimally. We thus develop the “Pathway Ensemble Tool” (PET), which outperforms existing methods. Deploying PET, we identify prognostic pathways across 12 cancer types. PET-identified prognostic pathways offer additional insights, with genes within these pathways serving as reliable biomarkers for clinical outcomes. Additionally, normalizing these pathways using drug repurposing strategies represents therapeutic opportunities. For example, the top predicted repurposed drug for bladder cancer, a CDK2/9 inhibitor, represses cell growth in vitro and in vivo. We anticipate that using Benchmark and PET for unbiased pathway discovery will offer additional insights into disease mechanisms across a spectrum of diseases, enabling biomarker discovery and therapeutic strategies.
