Simultaneous Imaging of Tumor and Host Cells in the Microenvironment
微环境中肿瘤和宿主细胞的同步成像
基本信息
- 批准号:10549299
- 负责人:
- 金额:$ 3.36万
- 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:2022-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:Adverse eventAffectAffinityAftercareAnnexinsAntibodiesAtlas of Cancer Mortality in the United StatesBindingBispecific AntibodiesBreast Cancer CellBreast Cancer DetectionBreast Cancer PatientBreast Cancer TreatmentBreast Cancer geneBreast Cancer therapyCancer BiologyCancer DetectionCancer EtiologyCancerousCause of DeathCellsCessation of lifeCirculationClinicalDetectionDiagnosisDiseaseDisease OutcomeDrug KineticsDyesERBB2 geneEquilibriumExhibitsFibroblastsFluorescenceFoundationsGoalsHistologicImageImage EnhancementImmuneImmunotherapeutic agentInterventionLesionLigandsLocalized DiseaseMalignant NeoplasmsMapsMeasuresMetastatic breast cancerMethodsMicroscopicMolecularMolecular ProbesMolecular TargetMonitorMusNear-infrared optical imagingNeoplasm MetastasisOpticsOutcomePatient-Focused OutcomesPatientsPenetrationPeptidesPharmaceutical PreparationsPhosphorylationPopulationPrediction of Response to TherapyProcessPrognosisPropertyQuality of lifeRecurrenceRecurrent diseaseRecurrent tumorRegional DiseaseReportingResearchResidual NeoplasmResidual stateSignal TransductionSpecificityStromal CellsSurvival RateTestingTherapeuticTimeTissuesTransgenic OrganismsTreatment outcomeTumor BiologyTumor TissueTumor VolumeWomanWorkcancer biomarkerscancer cellcancer imagingcancer therapycell typechemotherapydesigndetection methoddetection sensitivityeffective therapyfibroblast-activating factorfluorescence lifetime imagingfluorophoreimaging agentimaging modalityimaging platformimaging probeimprovedin vivoin vivo fluorescencemalignant breast neoplasmmicroscopic imagingmolecular imagingmortalitymouse modelneoplastic cellnoveloptical imagingoptimal treatmentsovertreatmentpersonalized medicinepre-clinicalprognosticprognostic indicatorside effectsmall moleculestandard of caretargeted agenttargeted biomarkertargeted imagingtargeted treatmenttraittreatment planningtreatment responsetriple-negative invasive breast carcinomatumortumor growthtumor microenvironment
项目摘要
Proposal Summary/Abstract
While there have been significant advances in the detection and treatment of breast cancer, mortality due to
metastatic disease recurrence remains unacceptably high and a leading cause of death. Furthermore,
chemotherapies with intolerable side effects remain the standard of care for metastatic breast cancer patients,
which is highly detrimental to quality of life. Advances in molecular targeting cancer imaging offer a window into
underlying tumor biology and support the use of individualized targeted therapies that can spare patients over-
treatment with harsh chemotherapies. However, most molecular imaging probes typically target either cancer
cells or, more recently, a single cell type in the tumor microenvironment. These approaches are inherently
limited in the information they can provide.
Optimal treatment planning relies on a complete picture of disease state, including microscopic regions of
residual disease and understanding the potential for recurrence based on a lesion’s specific molecular traits.
As such, the goal of this proposal is to provide the foundation for a clinically useful means to image and
understand disease status before, during, and after treatment of primary breast cancer and metastatic disease.
We postulate that molecular imaging of both the microenvironment and cancer cells simultaneously will provide
more complete detection of diseased regions and an understanding of dynamic changes in tumor
microenvironment that are needed to support personalized therapy.
We propose: (Aim1) A bispecific strategy targeting both breast cancer cells and cancer-associated fibroblasts
in the tumor microenvironment to enhance tumor detection. (Aim 2) Differentially targeting cancer cells and
cancer-associated fibroblasts with near-infrared molecular probes with similar spectral properties but different
fluorescent lifetime values to extract tumor-stroma ratio noninvasively, which is a prognostic indicator in breast
cancer. This non-invasive method of determining the relative abundance of malignant cells and cancer-
associated fibroblasts will be compared with the traditional histologic determination of tumor-stroma ratio.
At the completion of this study, we expect to have established a signal amplification method to detect small
cancerous lesions and a non-invasive approach to map cancer-stromal ratio to understand how the dynamic
changes in the tumor microenvironment affect cancer biology.
提案摘要/摘要
虽然在乳腺癌的检测和治疗方面已经取得了重大进展,但由于乳腺癌而导致的死亡率仍然很高。
转移性疾病的复发仍然高得不可接受,并且是死亡的主要原因。此外,委员会认为,
具有不可忍受的副作用的化疗仍然是转移性乳腺癌患者的标准治疗,
这对生活质量非常有害。分子靶向癌症成像的进展提供了一个窗口,
基础肿瘤生物学并支持使用个体化靶向治疗,可以让患者避免过度
用严厉的化疗来治疗。然而,大多数分子成像探针通常靶向癌症,
细胞或最近的肿瘤微环境中的单一细胞类型。这些方法本质上是
他们能提供的信息有限。
最佳的治疗计划依赖于疾病状态的完整图像,包括微观区域,
残留疾病和了解潜在的复发病变的基础上的具体分子性状。
因此,本提案的目标是为临床上有用的成像和
了解原发性乳腺癌和转移性疾病治疗前、治疗中和治疗后的疾病状态。
我们假设同时对微环境和癌细胞进行分子成像将提供
更完整地检测病变区域并了解肿瘤的动态变化
需要支持个性化治疗的微环境。
我们提出:(Aim 1)靶向乳腺癌细胞和癌症相关成纤维细胞的双特异性策略
在肿瘤微环境中增强肿瘤检测。(Aim 2)差异靶向癌细胞,
癌症相关成纤维细胞与近红外分子探针具有相似的光谱特性,但不同
非侵入性提取肿瘤-间质比率的荧光寿命值,这是乳腺癌的预后指标
癌这种确定恶性细胞和癌症相对丰度的非侵入性方法-
将相关的成纤维细胞与传统的肿瘤-间质比率的组织学测定进行比较。
在完成这项研究后,我们期望已经建立了一种信号放大方法来检测小的
癌性病变和一种非侵入性的方法来绘制癌症-间质比率,以了解动态
肿瘤微环境的变化影响癌症生物学。
项目成果
期刊论文数量(0)
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Megan Suzanne Michie其他文献
Megan Suzanne Michie的其他文献
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{{ truncateString('Megan Suzanne Michie', 18)}}的其他基金
Simultaneous Imaging of Tumor and Host Cells in the Microenvironment
微环境中肿瘤和宿主细胞的同步成像
- 批准号:
10387354 - 财政年份:2022
- 资助金额:
$ 3.36万 - 项目类别:
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