grant
Pre-clinical Development of Radiation Sensitizers for Patients with Glioblastoma
Organization DIVISION OF CLINICAL SCIENCES - NCILocation UNITED STATES
NIHUS FederalResearch GrantFY2025AOF2AffectAnimalsBBB penetrationBlood megakaryocyteC-K-RASCell BodyCell LineCellLineCellsCharacteristicsClinicClinicalClinical TrialsCollaborationsDNADNA mutationDNA-6-O-Methylguanine[protein]-L-Cysteine S-MethyltransferaseDeoxyribonucleic AcidDevelopmentDoseDrug KineticsDrugsDysfunctionEC 2.1.1.63FDA approvedFailureFunctional disorderGenetic ChangeGenetic defectGenetic mutationGlioblastomaGoalsGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaGuanine-O(6)-AlkyltransferaseHDAC AgentHDAC inhibitorHistone Deacetylase InhibitorHistone deacetylase inhibitionImageIn VitroIntermediary MetabolismK-RAS2AK-RAS2BK-RasK-Ras 2AK-Ras-2 OncogeneKDM1AKDM1A geneKRASKRAS2KRAS2 geneKi-RASLSD1Lysine-Specific Demethylase 1Lysine-Specific Demethylase 1AMGMTMGMT geneMedicationMegakaryocytesMegalokaryocyteMetabolic ProcessesMetabolismMethylated-DNA Protein-Cysteine MethyltransferaseMethylated-DNA-Protein-Cysteine S-MethyltransferaseMethylguanine-DNA Methyltransferase GeneModelingMolecularMutationNCATSNational Center for Advancing Translational SciencesO(6)-AGTO(6)-Alkylguanine-DNA AlkyltransferaseO(6)-MeG-DNA MethyltransferaseO(6)-Methylguanine DNA TransmethylaseO(6)-Methylguanine MethyltransferaseO(6)-Methylguanine-DNA MethyltransferaseO6-Alkylguanine DNA AlkyltransferaseOncogene K-RasPathway interactionsPatientsPharmaceutical PreparationsPharmacokineticsPharmacologyPhysiopathologyPreclinical dataPrimary NeoplasmPrimary TumorRASK2Radiation SensitizersRadiation therapyRadiation-Sensitizing AgentsRadiation-Sensitizing DrugsRadiosensitizing AgentsRadiosensitizing DrugsRadiotherapeuticsRadiotherapyRadiotherapy sensitizerReaction TimeRecurrenceRecurrentResponse RTResponse TimeRoleStrains Cell LinesTestingToxicologyTranslatingTranslationsWorkalkylguanine DNA alkyltransferaseblood-brain barrier penetrationbloodbrain barrier penetrationclinical relevanceclinically relevantcomputer based predictioncultured cell linedevelopmentaldrug/agentexperiencegenome mutationglioblastoma multiformeglioma cancer stem cellglioma cancer stem like cellglioma progenitorglioma stem cellsglioma stem like cellimagingimprovedin vivoinhibitorirradiationmetabolic imagingmethylguanine DNA methyltransferasenew markernovelnovel biomarkernovel markerpathophysiologypathwaypre-clinicalpre-clinical developmentpre-clinical studypreclinicalpreclinical developmentpreclinical findingspreclinical informationpreclinical studypredictive modelingprogramspsychomotor reaction timeradiation treatmentradiosensitizerresponsesocial rolespongioblastoma multiformetranslationtreatment with radiationtumorv-Ki-RAS2 Kirsten Rat Sarcoma 2 Viral Oncogene Homologwork-study
Description preview
This year we have focused on two pathways. The first is the KRAS pathway. We initially determined if any of our GBM cell lines or glioma stem-cell lines had the common KRAS mutation. They did not. So we focused on drugs that inhibit the function of intact KRAS. The in vitro work for this study is complete but we are unable to complete the animal…
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