| Literature DB >> 30146332 |
Elizabeth Stewart1, Justina McEvoy2, Hong Wang3, Xiang Chen4, Victoria Honnell1, Monica Ocarz5, Brittney Gordon5, Jason Dapper1, Kaley Blankenship6, Yanling Yang7, Yuxin Li8, Timothy I Shaw9, Ji-Hoon Cho10, Xusheng Wang10, Beisi Xu4, Pankaj Gupta4, Yiping Fan4, Yu Liu4, Michael Rusch4, Lyra Griffiths5, Jongrye Jeon5, Burgess B Freeman11, Michael R Clay12, Alberto Pappo6, John Easton4, Sheila Shurtleff12, Anang Shelat13, Xin Zhou4, Kristy Boggs4, Heather Mulder4, Donald Yergeau4, Armita Bahrami12, Elaine R Mardis14, Richard K Wilson15, Jinghui Zhang4, Junmin Peng7, James R Downing12, Michael A Dyer16.
Abstract
Personalized cancer therapy targeting somatic mutations in patient tumors is increasingly being incorporated into practice. Other therapeutic vulnerabilities resulting from changes in gene expression due to tumor specific epigenetic perturbations are progressively being recognized. These genomic and epigenomic changes are ultimately manifest in the tumor proteome and phosphoproteome. We integrated transcriptomic, epigenomic, and proteomic/phosphoproteomic data to elucidate the cellular origins and therapeutic vulnerabilities of rhabdomyosarcoma (RMS). We discovered that alveolar RMS occurs further along the developmental program than embryonal RMS. We also identified deregulation of the RAS/MEK/ERK/CDK4/6, G2/M, and unfolded protein response pathways through our integrated analysis. Comprehensive preclinical testing revealed that targeting the WEE1 kinase in the G2/M pathway is the most effective approach in vivo for high-risk RMS.Entities:
Keywords: epigenetics; molecular targeted therapy; pediatric cancer; preclinical testing; proteomics; rhabdomyosarcoma
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Year: 2018 PMID： 30146332 PMCID： PMC6158019 DOI： 10.1016/j.ccell.2018.07.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743