Therapy for Metastatic breast cancer based on micro RNA silencing
基于微小RNA沉默的转移性乳腺癌治疗
基本信息
- 批准号:9979793
- 负责人:
- 金额:$ 58.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:AftercareAnatomyAnimal BehaviorApoptosisBiological AvailabilityBody WeightBrainBreast AdenocarcinomaBreast Cancer CellBreast cancer metastasisCancer PatientCell ProliferationCell SurvivalCellsClinicalDevelopmentDiseaseDisseminated Malignant NeoplasmDistantDistant MetastasisDoseDoxorubicinDrug KineticsEnzymesEvaluationFluorescence MicroscopyGoalsGonadotropin-Releasing Hormone ReceptorHistologyHistopathologyHumanImageInflammatoryInterferon-alphaInterleukin-6LifeLiverLungMagnetic Resonance ImagingMagnetic nanoparticlesMediatingMembraneMetastatic Neoplasm to the BoneMetastatic Neoplasm to the LiverMetastatic Neoplasm to the LungMetastatic breast cancerMetastatic malignant neoplasm to brainMetastatic toMicroRNAsMolecularNeoplasm MetastasisOligonucleotidesOncogenicOrganPalliative CarePatientsPeptidesPhysiologicalPlayPrimary NeoplasmProtocols documentationRNA InterferenceRelapseResearchRoleSalvage TherapySavingsSiteSpecificitySurvival AnalysisTNF geneTherapeuticTherapeutic EffectTimeToxic effectTreatment Efficacyactivating transcription factoranimal morbiditybasebioluminescence imagingbonecancer cellchemotherapycytokineeffectiveness evaluationin vitro testingin vivoin vivo imaginglocked nucleic acidlymph nodesmalignant breast neoplasmmigrationmortalitymouse modelnanodrugnanoparticlenanotherapyneoplastic cellnon-invasive imagingnovel strategiestherapeutic targettherapy outcometreatment responseuptake
项目摘要
Treatment options for patients with metastatic breast cancer are severely limited and ultimately rely on
palliative care representing an unmet clinical need. Previous studies have demonstrated that microRNAs play
a significant role in the formation of metastasis including those from breast cancer. Considering the paucity of
options for patients with metastasis from breast cancer, in this proposal we focused on targeting miR-10b
proven to be responsible for metastatic spread. While previous studies showed that miR-10b drives invasion
and migration of cancer cells from primary tumors, our recent discovery demonstrated that in metastatic cells it
is also responsible for cell viability and proliferation and that survival of metastatic cells crucially depends on
the high level of miR-10b expression. This discovery formed a cornerstone of our therapeutic strategy aimed at
specific eradication of metastatic tumor cells. This will be done using imaging-capable modular nanodrugs,
which distribute to lung, liver, bone, or brain metastases. These nanodrugs consist of magnetic nanoparticles
that carry locked-nucleic acid (LNA) oligonucleotides inhibiting microRNA-10b. Targeting moieties conjugated
to the nanoparticles facilitate their accumulation at distant metastatic sites. Previously we have demonstrated
the feasibility of the proposed approach. Delivery of the nanodrug to lymph nodes with already formed
metastases resulted in arrest of metastatic progression by inhibiting tumor cell proliferation and causing
apoptosis, which is a phenomenon that has not been described before. When treatment with the nanodrug was
combined with a low-dose of conventional chemotherapy (doxorubicin), there was regression and permanent
elimination of lymph node or lung metastases without relapse even after treatment was discontinued. Unlike
conventional chemotherapies, this therapeutic protocol was not associated with animal morbidity/mortality. In
the current application we propose to use the miR10b-inhibitory nanodrug in combination with low-dose
chemotherapy (where necessary) for targeting breast cancer metastases in distant organs. Noninvasive
imaging will be used to evaluate the delivery of the nanodrug. If successful, this approach could be a life-
extending (and possibly, life saving) alternative for patients with advanced metastatic disease for whom
salvage therapy is the only current option.
转移性乳腺癌患者的治疗选择严重受限,最终依赖于
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('ANNA MOORE', 18)}}的其他基金
Novel Prostate cancer therapy based on m-aconitase inhibition
基于 m-乌头酸酶抑制的新型前列腺癌疗法
- 批准号:
10435673 - 财政年份:2022
- 资助金额:
$ 58.65万 - 项目类别:
Novel Prostate cancer therapy based on m-aconitase inhibition
基于 m-乌头酸酶抑制的新型前列腺癌疗法
- 批准号:
10580844 - 财政年份:2022
- 资助金额:
$ 58.65万 - 项目类别:
Large Animal Facility for Imaging and Image-guided Therapies at MSU
密歇根州立大学用于成像和图像引导治疗的大型动物设施
- 批准号:
10373769 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
Therapy for Metastatic breast cancer based on micro RNA silencing
基于微小RNA沉默的转移性乳腺癌治疗
- 批准号:
10434241 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
anti-miR-10b Nanodrug for Treatment of Breast Cancer Metastasis: Study in Companion Animals
用于治疗乳腺癌转移的抗 miR-10b 纳米药物:伴侣动物研究
- 批准号:
10659027 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
anti-miR-10b Nanodrug for Treatment of Breast Cancer Metastasis: Study in Companion Animals
用于治疗乳腺癌转移的抗 miR-10b 纳米药物:伴侣动物研究
- 批准号:
10450168 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
Therapy for Metastatic breast cancer based on micro RNA silencing
基于微小RNA沉默的转移性乳腺癌治疗
- 批准号:
10489811 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
anti-miR-10b Nanodrug for Treatment of Breast Cancer Metastasis: Study in Companion Animals
用于治疗乳腺癌转移的抗 miR-10b 纳米药物:伴侣动物研究
- 批准号:
10265643 - 财政年份:2021
- 资助金额:
$ 58.65万 - 项目类别:
Therapy for Metastatic breast cancer based on micro RNA silencing
基于微小RNA沉默的转移性乳腺癌治疗
- 批准号:
9753181 - 财政年份:2018
- 资助金额:
$ 58.65万 - 项目类别:
siRNA Protection of Composite Islet Kidney Transplant in Baboons
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8970851 - 财政年份:2015
- 资助金额:
$ 58.65万 - 项目类别:
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