Project 1: Non-Invasive Clinical Assay for Early Detection of Treatment Resistance in Patients with Metastatic Prostate Cancer
项目1:早期检测转移性前列腺癌患者治疗耐药性的非侵入性临床检测
基本信息
- 批准号:10227729
- 负责人:
- 金额:$ 34.38万
- 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:2017-08-30 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAndrogen ReceptorAreaAwardBRCA2 geneBiological AssayBiological MarkersBiopsyBlood CirculationBlood TestsCancer PatientCarcinomaCastrationCellsClinicalCollectionDNADNA MethylationDNA Sequence AlterationDataDependenceDevelopmentDiseaseDisease ProgressionDreamsEarly DiagnosisEnrollmentFanconi Anemia Complementation Group A ProteinGenesGenomicsGoalsHeterogeneityInstitutional Review BoardsLeadLettersMalignant neoplasm of prostateMedicineMetastatic Prostate CancerNatureNeuroendocrine Prostate CancerNeurosecretory SystemsPTEN genePathologicPatient SelectionPatientsPatternPerformancePharmaceutical PreparationsPhenotypePlasmaPlatinumPopulationProgression-Free SurvivalsProspective cohortRB1 geneReceptor SignalingRefractory DiseaseResistanceSamplingSelection for TreatmentsSiteSpecimenTP53 geneTestingTimeTissuesVisceral metastasisWorkabirateroneadvanced diseaseadvanced prostate cancerassay developmentbasecancer clinical trialcastration resistant prostate cancercirculating DNAclinical developmentexome sequencinggenomic biomarkergenomic signaturehormone therapyimprovedindustry partnermemberneuroendocrine phenotypepatient subsetspredicting responseprognosticprospectivereceptor expressionsafe patienttargeted treatmenttherapy resistanttranscriptometumor
项目摘要
SUMMARY
Identifying patients with metastatic castration resistant prostate cancer (CRPC) that will no longer benefit from
potent androgen receptor (AR)-directed therapies is an unmet need. One mechanism involves loss of AR
signaling dependence and its early detection remains challenging. We have developed a genomic signature
associated with AR-independence and the neuroendocrine phenotype that can be detected non-invasively
using plasma samples from patients. In this proposal, we will develop a targeted assay applied to prospective
cohorts to assess tumor dynamics and clinical impact of AR-independent genomic alterations in predicting
response to subsequent AR-targeted therapies. We will also define the spectrum and pattern of circulating
tumor clones compared to matched biopsies in patients with metastatic CRPC using a whole exome
sequencing approach. This study would lead to further clinical development of a plasma genomic biomarker
with several areas of potential impact including early detection of patients transforming towards AR-
independence leading to early cessation of AR therapy and consideration of metastatic biopsy to look for
neuroendocrine transformation and platinum-based therapies.
总结
确定不再受益于前列腺癌治疗的转移性去势抵抗性前列腺癌(CRPC)患者
有效的雄激素受体(AR)导向疗法是一种未满足的需求。一种机制涉及AR的丢失
信号依赖性及其早期检测仍然具有挑战性。我们开发了一种基因组特征
与AR独立性和可以非侵入性检测的神经内分泌表型相关
使用病人的血浆样本。在这项提案中,我们将开发一种靶向检测方法,
队列,以评估肿瘤动力学和AR非依赖性基因组改变在预测
对后续AR靶向治疗的反应。我们还将定义循环的频谱和模式,
使用全外显子组比较转移性CRPC患者的肿瘤克隆与匹配活检
排序方法。这项研究将导致血浆基因组生物标志物的进一步临床开发
有几个潜在的影响领域,包括早期发现向AR转化的患者,
独立性导致早期停止AR治疗,并考虑转移性活检以寻找
神经内分泌转化和基于铂的疗法。
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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Himisha Beltran其他文献
Himisha Beltran的其他文献
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{{ truncateString('Himisha Beltran', 18)}}的其他基金
"DNMT and TET1 reprogramming as a targetable mechanism of resistance in advanced prostate cancer"
“DNMT 和 TET1 重编程作为晚期前列腺癌的靶向耐药机制”
- 批准号:
10681632 - 财政年份:2023
- 资助金额:
$ 34.38万 - 项目类别:
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate Cancer
前列腺癌中 EZH2 和 PARP 抑制反应和耐药性的分子决定因素
- 批准号:
10628273 - 财政年份:2023
- 资助金额:
$ 34.38万 - 项目类别:
Molecular mechanisms underlying lineage plasticity in prostate cancer
前列腺癌谱系可塑性的分子机制
- 批准号:
10375455 - 财政年份:2020
- 资助金额:
$ 34.38万 - 项目类别:
Molecular mechanisms underlying lineage plasticity in prostate cancer
前列腺癌谱系可塑性的分子机制
- 批准号:
10596605 - 财政年份:2020
- 资助金额:
$ 34.38万 - 项目类别:
Project 1: Non-Invasive Clinical Assay for Early Detection of Treatment Resistance in Patients with Metastatic Prostate Cancer
项目1:早期检测转移性前列腺癌患者治疗耐药性的非侵入性临床检测
- 批准号:
9357038 - 财政年份:
- 资助金额:
$ 34.38万 - 项目类别:
Project 1: Non-Invasive Clinical Assay for Early Detection of Treatment Resistance in Patients with Metastatic Prostate Cancer
项目1:早期检测转移性前列腺癌患者治疗耐药性的非侵入性临床检测
- 批准号:
9763525 - 财政年份:
- 资助金额:
$ 34.38万 - 项目类别:
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