Repurposing redox active agents for exploiting differences in cancer cell metabolism for improving cancer therapy
重新利用氧化还原活性剂,利用癌细胞代谢的差异来改善癌症治疗
基本信息
- 批准号:10019479
- 负责人:
- 金额:$ 15.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-17 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Antineoplastic AgentsAscorbic AcidAwardBiological MarkersBiologyCancer BiologyChemosensitizationChemotherapy and/or radiationClinicalClinical ResearchClinical TrialsCore FacilityDNA DamageDoseEnvironmentFree RadicalsFundingGlioblastomaGrantHydrogen PeroxideIn VitroIntravenousIonsIowaIronLeadershipLungMalignant NeoplasmsMeasuresMediatingMelissaMetabolicMetabolismMetalsModelingNatural Products ChemistryNon-Small-Cell Lung CarcinomaNormal CellOxidation-ReductionOxidative StressPharmacologic AscorbatePharmacologyPharmacy facilityPlant RootsPostdoctoral FellowProgram Research Project GrantsRadiation OncologyRadioRadiobiologyResearchResearch PersonnelResearch Project GrantsScientistSignal PathwaySulfhydryl CompoundsTestingToxic effectTrainingTranslational ResearchUniversitiesWagesWorkascorbatecancer cellcancer therapychemoradiationexperiencegenetic approachimprovedin vivoiron metabolismknowledge basemembernoveloxidationoxidative damagepancreatic cancer cellspreclinical studyprogramsradiation responseresponsetheoriestranslational studytumor metabolism
项目摘要
Abstract
Dr. Melissa Fath is currently 100% supported by the program project grant entitled “Exploiting Redox
Metabolism Using Pharmacological Ascorbate (P-AscH−) for Cancer Therapy” (P01 CA217797). The theme of
this P01 is exploiting cancer cell redox metabolism using pharmacological ascorbate (P-AscH-; high dose
intravenous vitamin C) for improving cancer therapy. The P01 is composed of 3 major research projects and 3
core facilities. The proposal is highly integrated and focused on preclinical, translational and clinical studies
relevant to the use of P-AscH− in cancer therapy and Dr. Fath's research will impact all three of the research
projects and two of the cores. This R50 application proposes 100 % salary support for Dr. Fath to support all
the projects and two cores in the P01 research program as well as any new research initiatives funded by NCI
that may arise from that work. The Unit Director of the current proposal, Dr. Douglas Spitz, is part of the multi-
PI leadership team as well as the principle investigator on Project 2, “Exploiting Labile Iron Pools for Improving
NSCLC Therapy Using Pharmacological Ascorbate”. Specifically Project 2 in the P01 will test the hypothesis
that P-AscH− selectively sensitizes non-small cell lung cancers to radiation and chemotherapy by selectively
increasing cancer cell steady-state levels of H2O2 as a result of specific disruptions in redox-active iron
metabolism mediated by endogenous levels of O2.-/H2O2 . The Free Radical and Radiation Biology Program
(FRRBP) in the Department of Radiation Oncology at the University of Iowa is an ideal scientific environment
for this proposed research because of its historic roots in radiation biology as well as the free radical theory of
cancer in association with a strong Radiation Oncology Department. Dr. Spitz is the division director of FRRBP
and Dr. Fath is an associate research scientist that has been an active collaborative member for over 10 years.
Dr. Fath has considerable expertise in testing the involvement of free radicals, thiol oxidation, redox sensitive
signaling pathways, and oxidative damage end-points in many studies exploiting manipulations of redox
metabolism to repurpose drugs for cancer therapy. Her background and training in Clinical Pharmacy,
Medicinal & Natural Products Chemistry, and Free Radical Cancer Biology make her ideally suited to work in
this highly collaborative and integrated group doing both in vitro and in vivo translational research as well as
supporting clinical trials. Dr. Fath will focus on the redox biology of O2·- and H2O2 as well as the involvement of
Fe metabolism in the differential effects of that mediate P-AscH- induced radio-chemotherapy sensitization.
She will quantify radio-chemo- sensitization, measure steady-state H2O2, study and manipulate labile iron
pools using both pharmacological and genetic approaches, and assess oxidative stress, and DNA damage
endpoints in cancer treatment models. In addition, Dr. Fath will be responsible for measuring biomarkers of
oxidative stress in the clinical trials and determining if they correlate to clinical responses. It is clear that Dr.
Fath's experience and expertise is invaluable to P01 CA217797 and she is well-qualified as a candidate for the
P50 award mechanism.
摘要
项目成果
期刊论文数量(0)
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Melissa Ann Fath其他文献
Melissa Ann Fath的其他文献
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{{ truncateString('Melissa Ann Fath', 18)}}的其他基金
Repurposing redox active agents for exploiting differences in cancer cell metabolism for improving cancer therapy
重新利用氧化还原活性剂,利用癌细胞代谢的差异来改善癌症治疗
- 批准号:
10478857 - 财政年份:2019
- 资助金额:
$ 15.51万 - 项目类别:
Repurposing redox active agents for exploiting differences in cancer cell metabolism for improving cancer therapy
重新利用氧化还原活性剂,利用癌细胞代谢的差异来改善癌症治疗
- 批准号:
10239057 - 财政年份:2019
- 资助金额:
$ 15.51万 - 项目类别:
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