Research Papers:

Alveolar rhabdomyosarcoma: morphoproteomics and personalized tumor graft testing further define the biology of PAX3-FKHR(FOXO1) subtype and provide targeted therapeutic options

Robert E. Brown _, Jamie Buryanek, Amanda M. Katz, Keren Paz and Johannes E. Wolff

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Oncotarget. 2016; 7:46263-46272. https://doi.org/10.18632/oncotarget.10089

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Robert E. Brown1, Jamie Buryanek1, Amanda M. Katz2, Keren Paz2, Johannes E. Wolff3

1Department of Pathology & Laboratory Medicine, UT Health, McGovern Medical School, Houston, TX 77025, USA

2Scientific Operations, Champions Oncology, Baltimore, MD 21205, USA

3Present address: Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA

Correspondence to:

Robert E. Brown, email: [email protected]

Keywords: alveolar rhabdomyosarcoma, PAX3-FKHR subtype, morphoproteomics, xenograft testing, targeted therapy

Received: April 08, 2016     Accepted: June 03, 2016     Published: June 15, 2016


Alveolar rhabdomyosarcoma (ARMS) represents a block in differentiation of malignant myoblasts. Genomic events implicated in the pathogenesis of ARMS involve PAX3-FKHR (FOXO1) or PAX7-FKHR (FOXO1) translocation with corresponding fusion transcripts and fusion proteins. Commonalities in ARMS include uncontrollable proliferation and failure to differentiate. The genomic-molecular correlates contributing to the etiopathogenesis of ARMS incorporate PAX3-FKHR (FOXO1) fusion protein stimulation of the IGF-1R, c-Met and GSK3-β pathways. With sequential morphoproteomic profiling on such a case in conjunction with personalized tumor graft testing, we provide an expanded definition of the biology of PAX3-FKHR (FOXO1) ARMS that integrates genomics, proteomics and pharmacogenomics. Moreover, therapies that target the genomic and molecular biology and lead to tumoral regression and/or tumoral growth inhibition in a xenograft model of ARMS are identified.

Significance: This case study could serve as a model for clinical trials using relatively low toxicity agents in both initial and maintenance therapies to induce remission and reduce the risk of recurrent disease in PAX3-FKHR (FOXO1) subtype of ARMS.

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