Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses.
Cancer Cell
; 34(3): 411-426.e19, 2018 09 10.
Article
in En
| MEDLINE
| ID: mdl-30146332
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rhabdomyosarcoma
/
Protein-Tyrosine Kinases
/
Nuclear Proteins
/
Biomarkers, Tumor
/
Cell Cycle Proteins
/
Muscle Neoplasms
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Prognostic_studies
Language:
En
Journal:
Cancer Cell
Year:
2018
Document type:
Article