Adipokine Signaling as a Therapeutically Targetable Driver of Tumor Metabolism
脂肪因子信号传导作为肿瘤代谢的治疗靶向驱动因素
基本信息
- 批准号:10580769
- 负责人:
- 金额:$ 35.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-05 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AdipocytesAllograftingAnimal ModelAutomobile DrivingBiological MarkersCarnitine Palmitoyltransferase ICatabolismCell DeathCell LineCellsCessation of lifeCharacteristicsClear cell renal cell carcinomaClinicalClustered Regularly Interspaced Short Palindromic RepeatsCytometryCytoplasmDataDepositionDevelopmentDiagnosticDoseEndocrine GlandsEpidemiologyFatty acid glycerol estersGenesGeneticGenetic TranscriptionGenetically Engineered MouseGlycogenGlycolysisHigh Fat DietHistologicHumanHypoxia Inducible FactorImageImmunocompetentIncidenceInflammatoryInterventionInvadedIronKDR geneKnockout MiceLeadLesionLinkLipidsMalignant NeoplasmsMediatingMetabolicMetabolic syndromeMetabolismMitochondriaModelingMolecularMonitorMonoclonal AntibodiesMusNatureNeoplasm TransplantationObesityOncogenicOutcomePF4 GenePathogenesisPatient-Focused OutcomesPatientsPharmacologyPhenotypeProductionProtein IsoformsProtein Tyrosine KinaseRadiation therapyRefractoryRegimenRegulationRenal Cell CarcinomaRenal carcinomaResistance developmentRisk FactorsRoleSamplingSignal TransductionSpecimenStressSystemTestingTherapeuticTherapeutically TargetableTissuesToxic effectTumor PromotionTumor Suppressor ProteinsTumor-infiltrating immune cellsTyrosine Kinase Inhibitoradipokinesangiogenesisautocrinecancer riskchemotherapydeprivationfatty acid transportgene repressionimprovedin silicolipid biosynthesislipid metabolismmultiple omicsneoplastic cellnovelnovel strategiesnovel therapeuticsoverexpressionoxidationparacrinepre-clinicalpreventprognosticreceptorresponserestorationsmall hairpin RNAstandard of caretargeted agenttargeted treatmenttransdifferentiationtumortumor growthtumor metabolismtumor-immune system interactionstumorigenesis
项目摘要
Project Summary:
The link between obesity and cancer is well-established epidemiologically, but poorly understood at a
mechanistic level. Clear cell renal cell carcinoma (ccRCC) is the most common form of renal cancer, and has
clear ties with metabolic syndrome. ccRCC simultaneously demonstrates drastic metabolic rewiring at the
histological and molecular levels that recently have been found to be essential for tumor development.
Currently, however, the standard of care for ccRCC is targeted therapeutics against tyrosine kinases including
the VEGF receptor, that in most cases lead to modest improvements in overall survival. Thus identification of
new approaches to treat ccRCC is needed, and altered metabolism may offer a clinically useful foothold. We
have investigated the characteristic lipid storage phenotype of ccRCC and identified a molecular mechanism
that is driven in part by obesity. The present application focusses on a soluble adipokine produced by fat and
tumors that suppresses lipid catabolism, and is essential for tumor growth. The very nature of a secreted
factor leads to both diagnostic and therapeutic potential, and here we investigate the impact of inhibiting the
adipokine, Chemerin, with multiple approaches including a monoclonal antibody in preclinical animal models of
ccRCC, and a genetically engineered mouse model (GEMM). We will also dissect the mechanisms of action of
Chemerin on tumor and non-tumor cells, and examine the significance of Chemerin isoforms in collected
clinical specimens. Together, the aim of the proposal is to validate a novel target in ccRCC that could be
combined with existing therapies to improve patient outcomes.
项目总结:
项目成果
期刊论文数量(0)
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Scott Michael Welford其他文献
Scott Michael Welford的其他文献
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{{ truncateString('Scott Michael Welford', 18)}}的其他基金
Adipokine Signaling as a Therapeutically Targetable Driver of Tumor Metabolism
脂肪因子信号传导作为肿瘤代谢的治疗靶向驱动因素
- 批准号:
10366023 - 财政年份:2021
- 资助金额:
$ 35.3万 - 项目类别:
Polyamine and Glutamate Driven Interactions in the Glioblastoma-Brain Microenvironment
胶质母细胞瘤-脑微环境中多胺和谷氨酸驱动的相互作用
- 批准号:
10317530 - 财政年份:2015
- 资助金额:
$ 35.3万 - 项目类别:
Polyamine Catabolism and Therapeutic Resistance in Glioblastoma Multiforme
多形性胶质母细胞瘤的多胺分解代谢和治疗耐药
- 批准号:
9122361 - 财政年份:2015
- 资助金额:
$ 35.3万 - 项目类别:
Polyamine and Glutamate Driven Interactions in the Glioblastoma-Brain Microenvironment
胶质母细胞瘤-脑微环境中多胺和谷氨酸驱动的相互作用
- 批准号:
10450174 - 财政年份:2015
- 资助金额:
$ 35.3万 - 项目类别:
A novel soluble receptor-based therapy for Kidney Cancer
一种基于可溶性受体的新型肾癌疗法
- 批准号:
8751723 - 财政年份:2014
- 资助金额:
$ 35.3万 - 项目类别:
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