Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer
项目3:巨噬细胞在卵巢癌抗VEGF药物耐药中的作用
基本信息
- 批准号:10251116
- 负责人:
- 金额:$ 34.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-22 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesAntibody TherapyAntitumor ResponseBiologicalBone MarrowCSF1R geneCancer CenterCancer PatientClinicalClinical ResearchDataDiffuseDisease-Free SurvivalDoctor of MedicineDrug CombinationsDrug TargetingEffectivenessGiant Cell TumorsGrowthHarvestHypoxiaITGAM geneImmuneInfiltrationLightMalignant NeoplasmsMalignant neoplasm of ovaryMeasuresMediatingMethodsMyeloid-derived suppressor cellsNeoplasm MetastasisOutcomeOvarianPathway interactionsPatientsPharmaceutical PreparationsPhasePhase II Clinical TrialsPlayPre-Clinical ModelRandomizedRegulationReportingResistanceRoleSignal PathwaySolid NeoplasmSupplementationSuppressor-Effector T-LymphocytesTestingTreatment FactorTumor-associated macrophagesVascular Endothelial Growth FactorsWorkangiogenesisbevacizumabclinical applicationclinical efficacyefficacy testingimprovedin vivoinhibitor/antagonistmacrophagemouse modelnovelrecruitresponsetherapy resistanttumortumor growthtumor microenvironment
项目摘要
Project 3 SUMMARY/ABSTRACT
Angiogenesis is known to play a critical role in cancer growth and metastasis. Among the many potential
targets, vascular endothelial growth factor (VEGF) has been well recognized to play an important role in
angiogenesis, and drugs targeting this pathway have been used against ovarian and other cancers. Clinical
use of anti-VEGF therapy, however, has yielded only modest improvement in progression-free or overall
survival of patients with ovarian cancer, likely due to adaptive changes in the tumor microenvironment. There
remains an unmet need to develop methods to enhance efficacy of anti-VEGF therapy and block growth-
promoting adaptive changes. The mechanisms of adaptive resistance to anti-VEGF treatment are largely
unknown. Understanding the adaptive resistance to anti-VEGF treatment has the potential to significantly
enhance the efficacy of anti-VEGF therapy in ovarian cancer patients. Our preliminary findings suggest that
tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are substantially
increased in the anti-VEGF therapy-resistant tumors and TAM depletion (with CSF1R inhibitor) can improve
the effectiveness of anti-VEGF therapy; however, the mechanisms by which this occurs are not well
understood. In this proposal, we will explore the mechanisms by which macrophages contribute to adaptive
resistance to anti-VEGF treatment and test the efficacy of dual targeting of VEGF and TAMs/MDSCs. Our
central hypothesis is that targeting TAMs in the microenvironment will reverse the immunophenotypical
alterations induced by bevacizumab and improve clinical efficacy. We will conduct a novel, induction,
randomized supplementation clinical study to assess the impact of adding a CSF1R inhibitor to identify and
overcome these effects as measured by objective response and event-free survival. The proposed work is
highly translational and has the potential to significantly enhance the efficacy of anti-VEGF therapy in ovarian
cancer patients.
项目3摘要/摘要
项目成果
期刊论文数量(0)
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{{ truncateString('ANIL K SOOD', 18)}}的其他基金
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- 批准号:
9754614 - 财政年份:2017
- 资助金额:
$ 34.45万 - 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
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- 批准号:
9979631 - 财政年份:2017
- 资助金额:
$ 34.45万 - 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
- 批准号:
9388779 - 财政年份:2017
- 资助金额:
$ 34.45万 - 项目类别:
Harnessing the power of exosomes for non-coding RNA delivery
利用外泌体的力量进行非编码 RNA 递送
- 批准号:
10670211 - 财政年份:2017
- 资助金额:
$ 34.45万 - 项目类别:
Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer
项目3:巨噬细胞在卵巢癌抗VEGF药物耐药中的作用
- 批准号:
10005297 - 财政年份:2017
- 资助金额:
$ 34.45万 - 项目类别:
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