Overcoming Breast Cancer Therapeutic Resistance by Multifunctional RNA Nanoparticles
通过多功能RNA纳米颗粒克服乳腺癌治疗耐药性
基本信息
- 批准号:10771651
- 负责人:
- 金额:$ 5.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-07 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Antiestrogen TherapyBreast Cancer CellBreast Cancer PatientBreast Cancer TreatmentBreast Cancer therapyCause of DeathCessation of lifeClinicalClinical TrialsCollaborationsDataDevelopmentDisease-Free SurvivalEstrogen AntagonistsEstrogen receptor positiveExhibitsHumanIn VitroKnowledgeLeadLegal patentMalignant NeoplasmsMedicineMissionNanotechnologyNewly DiagnosedOligonucleotidesPatient CarePatient-derived xenograft models of breast cancerPatientsPersonsPhasePre-Clinical ModelPrivate SectorPublic HealthRNARNA vaccineRadiation therapyResearchResistanceScientific Advances and AccomplishmentsSmall Business Technology Transfer ResearchTestingTherapeuticTissuesToxic effectTreatment EfficacyUnited States National Institutes of HealthUniversitiesUntranslated RNAWomanWorkanticancer researchchemotherapyeffective therapyefficacy testingimprovedin vivoinnovationmalignant breast neoplasmnanoparticlenanotherapeuticnext generationoverexpressionresistance genesafety assessmentside effecttargeted treatmenttherapy resistanttumor
项目摘要
Project Summary
Breast cancer is one of the most frequent cancers and leading causes of death for women in the
U.S. with an estimated 287,850 new diagnoses of invasive breast cancer and 43,250 deaths in 2022. The vast
majority (75%) of breast cancer is estrogen receptor-positive (ER+) breast cancer but unfortunately, about 50%
of them become resistant and fail to respond to the current anti-estrogen therapies. There are currently no
effective treatment approaches available for these therapeutic resistant breast cancer and patients often rely
on highly toxic chemo- and radiation therapies, etc. Thus, the development of new and improved targeted
treatment to overcome resistance and minimize side effects is urgently needed. Recent work has
established tissue-specific ER coactivator MED1 as a key anti-estrogen treatment resistance gene in breast
cancer. Importantly, MED1 is overexpressed in about 50% of all breast cancers and clinical evidence indicates
that MED1 expression highly correlates with poor disease-free survival of breast cancer patients. RNA
Nanotherapeutics and its research partners at the University of Cincinnati have developed an innovative
patented RNA nanotechnology-based approach to target MED1 in breast cancer cells to overcome treatment
resistance. These highly stable multifunctional RNA nanoparticles have been successfully tested in in vitro and
in vivo preclinical models and exhibited highly desirable tumor-specific targeting and treatment efficacy with no
apparent toxicity. In this Phase I STTR, RNA Nanotherapeutics, in collaboration with its research partners at
the University of Cincinnati and an oligonucleotide therapeutics CMC/strategy consultant, will carry out the
following specific aims: 1) test the efficacy of the pRNA-HER2apt-siMED1 nanoparticles in vivo in breast
cancer patient-derived xenograft (PDX) models; and 2) assess the safety and toxicity of the pRNA-HER2apt-
siMED1 nanoparticles in vivo. We expect successful completion of these proposed studies will provide the
results and data needed for our Phase II efforts and further engagement with private-sector investors to carry
out IND enabling studies for clinical trials. With the recent increased FDA approvals and broad use of RNA-
based vaccines and medicines, we fully anticipate that our RNA nanotechnology-based product represents a
highly promising next-generation therapy to benefit breast cancer patient care and beyond.
项目摘要
乳腺癌是世界上最常见的癌症之一,也是妇女死亡的主要原因。
美国估计2022年将有287,850例新诊断为浸润性乳腺癌,43,250例死亡。绝
大多数(75%)乳腺癌是雌激素受体阳性(ER+)乳腺癌,但不幸的是,约50%
他们中的一些人变得有抵抗力,并且对目前的抗雌激素疗法没有反应。目前没有
可用于这些治疗抗性乳腺癌的有效治疗方法和患者通常依赖于
因此,开发新的和改进的靶向治疗方法,
迫切需要克服耐药性和尽量减少副作用的治疗。最近的工作已经
建立了组织特异性ER辅激活因子MED 1作为乳腺癌中关键的抗雌激素治疗抗性基因
癌重要的是,MED 1在约50%的乳腺癌中过表达,临床证据表明,
MED 1表达与乳腺癌患者的无病生存率低高度相关。RNA
纳米治疗学及其在辛辛那提大学的研究伙伴已经开发出一种创新的
基于RNA纳米技术的专利方法,靶向乳腺癌细胞中的MED 1,以克服治疗
阻力这些高度稳定的多功能RNA纳米颗粒已在体外成功测试,
在体内临床前模型,并表现出非常理想的肿瘤特异性靶向和治疗效果,没有
明显毒性在第一阶段STTR中,RNA Nanotherapeutics与其研究伙伴合作,
辛辛那提大学和寡核苷酸治疗CMC/战略顾问,将进行
1)测试pRNA-HER 2apt-siMED 1纳米颗粒在乳腺癌中的体内功效,
癌症患者来源的异种移植物(PDX)模型;和2)评估pRNA-HER 2apt-1的安全性和毒性。
体内siMED 1纳米颗粒。我们预期这些拟议研究如能顺利完成,
我们的第二阶段工作所需的结果和数据,以及与私营部门投资者的进一步接触,
IND使临床试验研究成为可能。随着最近FDA批准的增加和RNA的广泛使用,
基于RNA的疫苗和药物,我们完全预计,我们的基于RNA纳米技术的产品代表了
非常有前途的下一代治疗,以造福乳腺癌患者的护理和超越。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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{{ truncateString('Xiaoting Zhang', 18)}}的其他基金
Overcoming Breast Cancer Therapeutic Resistance by Multifunctional RNA Nanoparticles
通过多功能RNA纳米颗粒克服乳腺癌治疗耐药性
- 批准号:
10600748 - 财政年份:2022
- 资助金额:
$ 5.5万 - 项目类别:
Role of MED1 in HER2-driven Breast Tumorigenesis
MED1 在 HER2 驱动的乳腺肿瘤发生中的作用
- 批准号:
8944439 - 财政年份:2015
- 资助金额:
$ 5.5万 - 项目类别:
Role of MED1 in HER2-driven Breast Tumorigenesis
MED1 在 HER2 驱动的乳腺肿瘤发生中的作用
- 批准号:
9095298 - 财政年份:2015
- 资助金额:
$ 5.5万 - 项目类别:
Role of MED1 in HER2-mediated tumorigenesis
MED1 在 HER2 介导的肿瘤发生中的作用
- 批准号:
10445621 - 财政年份:2015
- 资助金额:
$ 5.5万 - 项目类别:
Role of MED1 in HER2-mediated tumorigenesis
MED1 在 HER2 介导的肿瘤发生中的作用
- 批准号:
10600067 - 财政年份:2015
- 资助金额:
$ 5.5万 - 项目类别:
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