Abstract
Currently, even with intensive multimodal treatment, 20% of children and adolescents with cancer will still die due to disease and over 40% of survivors develop sequelae that affect the adult quality of life. Therefore, more effective and safer treatment options for children with cancer are still needed to increase cure rates, decrease toxicity and to minimize the risk of long term effects on survivors. The biology of pediatric cancers are intrinsically associated with dysregulation of signaling pathways that control normal embryonic development. Among these pathways are Wnt, Shh and Notch, and TGF-², which also play an important role in carcinogenesis and are involved in tumor chemo-and radio-resistance. The study of these pathways in the context of the biology of pediatric tumors may constitute a new field for the identification of target genes and understanding of the long-term effects caused by the different treatment modalities of infant tumors. Thus, this project aims to identify co-expression networks associated with the transcriptional modules of the above mentioned pathways in different pediatric tumors (medulloblastoma, ependymoma, Ewing's sarcoma and adrenal carcinoma). From these data, genes considered plausible therapeutic targets (those previously studied by our group, those with therapeutic/prognostic value established in the literature or genes that have a promising scientific value for each studied tumor) will be validated and subsequently investigated in in vitro and in vivo models through different techniques. This research may provide new molecular perspectives, both to elucidate the specific mechanisms involved in pediatric tumor biology, as for the identification of new therapeutic strategies for treating this cohort. (AU)
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