Narendran, AruSingh, Anjali2016-04-082016-04-0820162016Singh, A. (2016). Targeting Selective Receptor Tyrosine Kinases in Refractory Embryonal Tumors of Childhood (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27978http://hdl.handle.net/11023/2884Embryonal tumors are a collection of biologically heterogeneous malignancies and the exact cellular origin of these tumors is not known. Neuroblastoma (NB) and atypical teratoid/rhabdoid tumor (AT/RT) are highly malignant tumors of embryonal origin that primarily affect infants and young children. Neuroblastoma is the most common type of extra cranial solid tumor in children. In the case of AT/RT, the survival rate of children affected by this disease is the lowest when compared to all embryonal tumors. Despite intensifying multimodal treatments, children affected with refractory AT/RT and NB have unacceptably high treatment failure and mortality rates. To improve the clinical outcome of these malignancies, it is important to identify the key molecules and cellular pathways responsible for tumor progression, survival and invasion. Many childhood cancers have high activation levels of selective receptor tyrosine kinase signaling pathways. Activation of these signaling pathways promotes cell proliferation, differentiation and cell survival. Therefore, receptor tyrosine kinases (RTKs) have become attractive therapeutic targets and the use of small molecule kinase inhibitors to block their signal transduction functions has led to the discovery of a number of novel therapeutics agents. This research presents the relevant background information on two pediatric neoplasms that we have selected to study and aims to provide the rationale for the development of useful new therapies for their treatment. Presented in details are the data with respect to the establishment of a screening approach to identify effective therapeutic agents with information on target validation and target modulation activities that can be utilized to design future clinical trials for these cancers.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.OncologyPediatric Oncologydoctoral thesis10.11575/PRISM/27978