Alveolar rhabdomyosarcoma: morphoproteomics and personalized tumor graft testing further define the biology of PAX3-FKHR(FOXO1) subtype and provide targeted therapeutic options.
Oncotarget
; 7(29): 46263-46272, 2016 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-27323832
ABSTRACT
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-ß 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Tecidos Moles
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Protocolos de Quimioterapia Combinada Antineoplásica
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Rabdomiossarcoma Alveolar
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Medicina de Precisão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Child
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article