Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine.

Autor:	Schwark K; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Messinger D; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Cummings JR; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Bradin J; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Kawakibi A; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Babila CM; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Lyons S; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Ji S; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Cartaxo RT; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Kong S; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Cantor E; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Koschmann C; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Yadav VN; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States.; Department of Pediatrics, Children's Mercy Research Institute (CMRI), Kansas, MO, United States.; Department of Pediatrics, University of Missouri Kansas City School of Medicine, Kansas, MO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Aug 01; Vol. 12, pp. 922928. Date of Electronic Publication: 2022 Aug 01 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.922928
Abstrakt:	Pediatric high-grade glioma (pHGG), including both diffuse midline glioma (DMG) and non-midline tumors, continues to be one of the deadliest oncologic diagnoses (both henceforth referred to as "pHGG"). Targeted therapy options aimed at key oncogenic receptor tyrosine kinase (RTK) drivers using small-molecule RTK inhibitors has been extensively studied, but the absence of proper in vivo modeling that recapitulate pHGG biology has historically been a research challenge. Thankfully, there have been many recent advances in animal modeling, including Cre-inducible transgenic models, as well as intra-uterine electroporation (IUE) models, which closely recapitulate the salient features of human pHGG tumors. Over 20% of pHGG have been found in sequencing studies to have alterations in platelet derived growth factor-alpha (PDGFRA), making growth factor modeling and inhibition via targeted tyrosine kinases a rich vein of interest. With commonly found alterations in other growth factors, including FGFR, EGFR, VEGFR as well as RET, MET, and ALK, it is necessary to model those receptors, as well. Here we review the recent advances in murine modeling and precision targeting of the most important RTKs in their clinical context. We additionally provide a review of current work in the field with several small molecule RTK inhibitors used in pre-clinical or clinical settings for treatment of pHGG. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Schwark, Messinger, Cummings, Bradin, Kawakibi, Babila, Lyons, Ji, Cartaxo, Kong, Cantor, Koschmann and Yadav.)
Databáze:	MEDLINE
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