Department of Pediatrics; Division of Hematology/Oncology, Department of Pediatrics
Amino Acids, Peptides, and Proteins | Cancer Biology | Enzymes and Coenzymes | Neoplasms | Pediatrics
BACKGROUND: Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS: Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS: Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS: Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
DDR2, Kinase inhibitor, Neuroblastoma, RET, RTK
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DOI of Published Version
Rozen EJ, Shohet JM. Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology. Cancer Metastasis Rev. 2022 Mar;41(1):33-52. doi: 10.1007/s10555-021-10001-7. Epub 2021 Oct 30. PMID: 34716856; PMCID: PMC8924100. Link to article on publisher's site
Cancer metastasis reviews
Rozen EJ, Shohet JM. (2021). Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology. Open Access Publications by UMass Chan Authors. https://doi.org/10.1007/s10555-021-10001-7. Retrieved from https://escholarship.umassmed.edu/oapubs/4991
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.