Validation of predictive liquid biomarkers for patients with metastatic prostate cancer
转移性前列腺癌患者预测液体生物标志物的验证
基本信息
- 批准号:10409749
- 负责人:
- 金额:$ 16.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AR geneAcetatesAddressAdenocarcinomaAftercareAndrogen ReceptorAppearanceAreaBiological AssayBiological MarkersBiological Response Modifier TherapyBiomedical EngineeringBiopsyBloodBlood CellsBlood CirculationCLIA certifiedCancer CenterCancer PatientCategoriesCellsCellular AssayCentrifugationCertificationClinicalClinical ResearchClinical TrialsClonal ExpansionCollaborationsDNAData AnalysesDetectionDevelopmentDiagnosticDiseaseDisease ResistanceEarly DiagnosisEarly identificationEnhancersEnsureEvaluationEvolutionExclusionExposure toFailureFoundationsFrequenciesFutureGene ExpressionGene Expression ProfileGene Expression ProfilingGenesGenetic TranscriptionGoalsHistologicHygieneInstitutionLaboratoriesLeftLigand Binding DomainLiquid substanceLiverMagnetismMalignant NeoplasmsMalignant neoplasm of prostateMeasurementMemorial Sloan-Kettering Cancer CenterMessenger RNAMetastatic Prostate CancerMethodsMolecularMutationNeoplasm Circulating CellsNeuroendocrine Prostate CancerNeuroendocrine TumorsOutputPatient CarePatientsPerformancePopulationPreparationProbabilityProcessPrognosisProgression-Free SurvivalsProspective StudiesProtein AnalysisProvengeRNARNA SplicingRadiumRandomized Clinical TrialsReagentReceptor SignalingRecommendationResearch PersonnelResistanceResistance developmentRiskSamplingSiteSpecificitySurface PropertiesSurface TensionSystemSystematic BiasTechnologyTestingTherapeuticTimeTissuesTubeUniversitiesValidationVariantWisconsinabirateroneadvanced prostate cancerbasebonecancer biomarkerscancer cellcastration resistant prostate cancerchemotherapyclinically relevantcohortdiagnostic accuracydiagnostic tooldrug developmentenzalutamidehormone therapyimprovedinhibitorliquid biopsylymph nodesmennovel diagnosticsnovel therapeuticsoptimal treatmentsparticlepatient biomarkerspatient subsetsprecision medicinepredictive markerprognosticprognostic of survivalprognostic valueprospectiveradiological imagingresearch clinical testingresistance mechanismresponsesuccesstargeted treatmenttaxanetherapy resistanttooltreatment strategytreatment stratificationtumorvirtual
项目摘要
Project Summary/Abstract
The University of Wisconsin Carbone Cancer Center (UWCCC), Duke University and Memorial Sloan Kettering
Cancer Center (MSKCC) seek support for establishing the analytical and clinical validity of a Circulating Tumor
Cell (CTC) biomarker assay via the UH2/UH3 mechanism. This biomarker assay will evaluate a gene expression
signature of treatment resistant, castration-resistant prostate cancer (CRPC).
While many patients with prostate cancer benefit from Androgen Receptor Signaling Inhibitors (ARSIs), a subset
of patients do not respond to this class of treatments while nearly all others develop resistance within 1-2 years.
Identified mechanisms of resistance include development of Neuroendocrine Prostate Cancer (NEPC) and
expression of Androgen Receptor Splicing Variants (AR-Vs). Early detection of NEPC or AR-Vs as drivers of
treatment resistant prostate cancer would eliminate the need to wait for clinical manifestations of resistance,
accelerating the time to administration of more suitable therapy and increasing survival.
While precision medicine approaches are increasing in popularity and reliability, their ultimate capacity to
improve patient care hinges on their diagnostic accuracy. Realization of a clinically relevant assay requires
thorough analytical and clinical evaluation, and while many biomarker assays have successfully demonstrated
analytical performance, failure to address clinical utility has left many unable to improve on existing diagnostics.
By focusing our efforts on evaluation of both analytical and clinical validity, we aim to provide diagnostic accuracy
in assessing an expression of NEPC and AR-Vs, building a necessary foundation for future clinical trials.
To that end, we have optimized a multi-plexed gene expression assay on CTCs, that identifies these two major
categories of resistance to ARSIs. This assay has shown promising initial results in a preliminary cohort of
patients with aggressive CRPC. Optimization of this assay has taken into consideration the rarity of CTCs and
the diversity of other blood cells in circulation; ensuring efficient RNA extraction, probe specificity, and
appropriate data interpretation. The manipulation and retention of rare cells is enabled by our Exclusion-based
Sample Preparation (ESP) technology, wherein centrifugation and wash steps are eliminated. This automated
and commercially available platform, also called the Gilson ExtractMax, offers minimal user variability, thus
maximizing precision. Our collaboration with Dr. Kaitlin Sundling at the Wisconsin State Lab of Hygiene, a CAP-
approved clinical testing laboratory, provides expert oversight for planning and execution of analytical validation.
In collaboration with Dr. Andrew Armstrong, Dr. Susan Halabi and Dr. Dana Rathkopf, we have assembled a
team of clinical researchers and biostatisticians to rapidly validate this multi-plexed biomarker in a prospective
study. This RNA-based CTC assay shows potential for identifying treatment resistant prostate cancer in
preliminary studies of patients and is thus poised for success in both analytical and clinical validation.
项目总结/文摘
项目成果
期刊论文数量(1)
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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Andrew J Armstrong其他文献
Reply to M. K. Bos et al.
回复 M.K. Bos 等人。
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:45.3
- 作者:
J. Sperger;F. Feng;Andrew J Armstrong;Shuang G Zhao;J. Lang - 通讯作者:
J. Lang
Intensification of Androgen Deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer
转移性激素敏感前列腺癌的强化雄激素剥夺疗法
- DOI:
10.1016/j.yao.2023.12.006 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Jeffrey W. Shevach;Joseph J. Park;Andrew J Armstrong - 通讯作者:
Andrew J Armstrong
Reply to L. Dirix, B. De Laere et al, and A. Sharp et al.
回复 L. Dirix、B. De Laere 等人和 A. Sharp 等人。
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:45.3
- 作者:
Andrew J Armstrong;S. Halabi;Jun Luo;D. Nanus;H. Scher;E. Antonarakis;Daniel J. George - 通讯作者:
Daniel J. George
PROMISE Registry: A prostate cancer registry of outcomes and germline mutations for improved survival and treatment effectiveness
PROMISE 登记处:前列腺癌结果和种系突变登记处,以提高生存率和治疗效果
- DOI:
10.1002/pros.24650 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
C. Paller;Pedro C Barata;J. Lorentz;L. Appleman;Andrew J Armstrong;Tiffani A DeMarco;R. Dreicer;Jo Ann B Elrod;Mark T. Fleming;Christopher M. George;Elizabeth I. Heath;Maha H. Hussain;S. Mao;Rana R McKay;Alicia K Morgans;Matthew Orton;R. Pili;Elyn Riedel;B. Saraiya;J. Sigmond;Alexandra O. Sokolova;Walter M. Stadler;Christina Tran;Natalie Macario;Jacob Vinson;Rebecca Green;Heather H Cheng - 通讯作者:
Heather H Cheng
Reply to M.A.N. Şendur et al and J. Michels.
回复 M.A.N. 等人和 J. Michels。
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:45.3
- 作者:
D. Penson;Andrew J Armstrong;R. Concepcion;N. Agarwal;C. Olsson;L. Karsh;C. Dunshee;Fong Wang;Kenneth Wu;A. Krivoshik;D. Phung;C. Higano - 通讯作者:
C. Higano
Andrew J Armstrong的其他文献
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{{ truncateString('Andrew J Armstrong', 18)}}的其他基金
Validation of predictive liquid biomarkers for patients with metastatic prostate cancer
转移性前列腺癌患者预测液体生物标志物的验证
- 批准号:
10840022 - 财政年份:2021
- 资助金额:
$ 16.02万 - 项目类别:
Validation of predictive liquid biomarkers for patients with metastatic prostate cancer
转移性前列腺癌患者预测液体生物标志物的验证
- 批准号:
10214744 - 财政年份:2021
- 资助金额:
$ 16.02万 - 项目类别:
Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPC
男性 mCRPC 一线雄激素受体抑制剂治疗结果的临床基因组预测模型
- 批准号:
10620612 - 财政年份:2020
- 资助金额:
$ 16.02万 - 项目类别:
Clinical genomic predictive model of first line androgen receptor inhibitor therapy outcomes in men with mCRPC
男性 mCRPC 一线雄激素受体抑制剂治疗结果的临床基因组预测模型
- 批准号:
10264941 - 财政年份:2020
- 资助金额:
$ 16.02万 - 项目类别:
Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancer
AR抑制过程中靶向汇聚致癌信号以克服前列腺癌的转移和免疫逃避
- 批准号:
10224136 - 财政年份:2019
- 资助金额:
$ 16.02万 - 项目类别:
Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancer
AR抑制过程中靶向汇聚致癌信号以克服前列腺癌的转移和免疫逃避
- 批准号:
10475039 - 财政年份:2019
- 资助金额:
$ 16.02万 - 项目类别:
Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancer
AR抑制过程中靶向汇聚致癌信号以克服前列腺癌的转移和免疫逃避
- 批准号:
10665659 - 财政年份:2019
- 资助金额:
$ 16.02万 - 项目类别:
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