HCC Ovarian Cancer SPORE
HCC 卵巢癌孢子
基本信息
- 批准号:10713050
- 负责人:
- 金额:$ 216.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdvocateAmericanArchivesBRCA1 geneBioinformaticsBiometryBromodomains and extra-terminal domain inhibitorCancer CenterCancer EtiologyCancer PatientCarboplatinCell Cycle CheckpointCell Cycle Checkpoint GenesCellsCessation of lifeChemoresistanceClinicalClinical DataClinical TrialsCollaborationsCost SharingDNA RepairDevelopmentDiagnosisDiseaseDisease ProgressionDisease ResistanceDoctor of PhilosophyDoseEZH2 geneEnsureEpigenetic ProcessErinaceidaeExclusionExperimental ModelsFundingFutureGenerationsGoalsHumanImmuneImmune checkpoint inhibitorImmunotherapyIn VitroIncidenceIndividualInstitutionInvestmentsMalignant NeoplasmsMalignant neoplasm of ovaryMediatingMesenchymal Stem CellsMinority GroupsMitoticModelingMolecularMyeloid-derived suppressor cellsNew AgentsNewly DiagnosedOperative Surgical ProceduresPathologyPatient CarePatient-Focused OutcomesPatientsPennsylvaniaPhasePhase Ib TrialPlatinumPoly(ADP-ribose) Polymerase InhibitorPositioning AttributePrediction of Response to TherapyPrincipal InvestigatorPrognosisProgram Research Project GrantsProteinsRecurrenceRelapseResearchResearch InfrastructureResearch PersonnelResistanceResource SharingScienceScientistSignal TransductionTOPBP1 GeneTechnologyTestingTimeTranslational ResearchUnderrepresented MinorityWomananticancer researchcancer carecareercareer developmentcheckpoint therapychemotherapydata resourcedesignexperiencehomologous recombinationimprovedimproved outcomein vivoinhibitorinhibitor therapyinnovationmortalitymultidisciplinarymultipotent stromal progenitornotch proteinnovel diagnosticsnovel therapeutic interventionnovel therapeuticspatient responsepersonalized medicinephase II trialpotential biomarkerpre-clinicalpreventprogramsrecruitresponsesmoothened signaling pathwaystem cellsstromal progenitorsuccesssynergismtherapeutic developmenttherapy resistanttissue resourcetreatment strategytumortumor microenvironment
项目摘要
PROJECT SUMMARY/ABSTRACT – OVERALL
Ovarian cancer (OvCa) has the third highest mortality to incidence ratio and is the fifth leading cause of cancer
death in American women. The typical disease course of a patient with OvCa spans four and a half years from
the time of diagnosis to death. During the course of patient care, acquired and innate resistance to our most
effective and promising therapies, such as chemotherapy, PARP inhibitor therapy, and immunotherapy, drives
disease progression. The overall goal of the UPMC Hillman Cancer Center (HCC) OvCa SPORE is to prevent
and/or overcome therapeutic resistance to improve patient survival. Each of the SPORE’s three Projects
evolved from the innovative concepts and findings of SPORE investigators. Each project involves a clinical trial
with a new agent. In addition, each project, through complementary investigator expertise, incorporates critical
translational aims to identify patients most likely to respond to therapy. Project 1 will assess the ability of
inhibitors of the epigenetic regulator EZH2 to prevent/overcome OvCa stromal progenitor cell-driven resistance
to platinum-based chemotherapy. Project 2 will determine whether BET inhibitors, which downregulate critical
DNA repair and cell cycle checkpoint proteins, can reverse resistance to PARP inhibitors. Project 3 will test
whether inhibitors of the hedgehog signaling pathway, which drives tumor immune exclusion, can improve
OvCa patient response to immune checkpoint inhibitor therapy. The HCC OvCa SPORE will include a Career
Enhancement Program (CEP) and Developmental Research Program (DRP) in order to both encourage early
career investigators to enter the field of translational OvCa research and engage more established
investigators in OvCa research. The CEP and the DRP, which are cost-shared and proactive at providing
research funding to investigators from under-represented minority groups, will provide a pipeline of potential
future SPORE Projects. All SPORE, CEP, and DRP Projects will be receive fiscal and scientific oversight from
an Administrative Core and support from two shared resource cores. The Translational Pathology Core will
collect, annotate, archive, and distribute biospecimens and clinical data derived from the more than 300 HCC
OvCa patients seen each year. It will also develop new preclinical experimental models that behave more like
human OvCa. The Biostatistics and Bioinformatics Core will aid in design and analysis of all studies, including
‘omic’ technologies that can provide molecular and spatial characterization of individual cells within a tumor.
The SPORE Projects will also be supported by established and new collaborators who are internal and
external to HCC. Combined, the SPORE projects, CEP, DRP, and cores are positioned, together with our
vertical collaborators, to improve the outcomes of patients with ovarian cancer. The findings generated by the
SPORE will be advanced through further collaboration and future non-SPORE funding.
项目概要/摘要——总体
卵巢癌 (OvCa) 的死亡率与发病率之比排名第三,是第五大癌症原因
美国女性 OvCa 患者的典型病程长达四年半。
从诊断到死亡的过程中,我们最大的后天和先天的抵抗力。
有效且有前景的疗法,如化疗、PARP 抑制剂疗法和免疫疗法,推动
UPMC Hillman 癌症中心 (HCC) OvCa SPORE 的总体目标是预防疾病进展。
和/或克服治疗耐药性以提高患者的生存率。
每个项目均由 SPORE 研究人员的创新概念和发现演变而来。
此外,每个项目都通过互补的调查员专业知识,纳入了关键的内容。
转化的目的是确定最有可能对治疗产生反应的患者,项目 1 将评估患者的能力。
表观遗传调节因子 EZH2 的抑制剂可预防/克服 OvCa 基质祖细胞驱动的耐药性
项目 2 将确定 BET 抑制剂是否会下调关键作用。
DNA 修复和细胞周期检查点蛋白可以逆转 PARP 抑制剂的耐药性,项目 3 将进行测试。
驱动肿瘤免疫排斥的刺猬信号通路抑制剂是否可以改善
OvCa 患者对免疫检查点抑制剂治疗的反应 HCC OvCa SPORE 将包括职业生涯。
增强计划(CEP)和发展研究计划(DRP),以鼓励早期
职业研究者进入转化性 OvCa 研究领域并吸引更多成熟的研究人员
CEP 和 DRP 的研究人员共同承担费用并积极提供服务。
为代表性不足的少数群体的研究人员提供研究经费,将提供潜在的渠道
未来的 SPORE 项目。所有 SPORE、CEP 和 DRP 项目都将接受来自以下机构的财政和科学监督。
一个管理核心和两个共享资源核心的支持。
收集、注释、存档和分发来自 300 多个 HCC 的生物样本和临床数据
每年都会见到 OvCa 患者,它还将开发新的临床前实验模型,其行为更像。
人类 OvCa。生物统计学和生物信息学核心将有助于所有研究的设计和分析,包括
“组学”技术可以提供肿瘤内单个细胞的分子和空间特征。
SPORE 项目还将得到内部和新的合作者的支持
SPORE 项目、CEP、DRP 和核心与我们的外部一起定位。
垂直合作者,以改善卵巢癌患者的结果。
SPORE 将通过进一步合作和未来的非 SPORE 资助来推进。
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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Ronald J Buckanovich其他文献
Phase I and Randomized Phase II Study of Ruxolitinib With Frontline Neoadjuvant Therapy in Advanced Ovarian Cancer: An NRG Oncology Group Study.
Ruxolitinib 联合一线新辅助治疗治疗晚期卵巢癌的 I 期和随机 II 期研究:NRG 肿瘤学小组研究。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:45.3
- 作者:
Charles N Landen;Ronald J Buckanovich;M. Sill;R. Mannel;J. Walker;P. DiSilvestro;Cara Mathews;D. Mutch;Marcia L Hernandez;Lainie P Martin;Erin Bishop;Sarah E Gill;Mary E Gordinier;Robert A. Burger;C. Aghajanian;Joyce F Liu;K. Moore;M. Bookman - 通讯作者:
M. Bookman
Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.
西地尼布和奥拉帕尼联合用药与奥拉帕尼治疗复发性铂敏感卵巢癌的随机 II 期研究的总生存期和更新的无进展生存期结果。
- DOI:
10.1093/annonc/mdz018 - 发表时间:
2019-04-01 - 期刊:
- 影响因子:0
- 作者:
Joyce F Liu;William T. Barry;Michael J. Birrer;J. Lee;Ronald J Buckanovich;G. Fleming;B. Rimel;M. Buss;S. Nattam;J. Hurteau;W. Luo;J. Curtis;C. Whalen;Elise C. Kohn;S. Ivy;Ursula A. Matulonis - 通讯作者:
Ursula A. Matulonis
Activity of cabozantinib (XL184) in advanced ovarian cancer patients (pts): Results from a phase II randomized discontinuation trial (RDT).
卡博替尼 (XL184) 在晚期卵巢癌患者 (pts) 中的活性:II 期随机停药试验 (RDT) 的结果。
- DOI:
10.1200/jco.2011.29.15_suppl.5008 - 发表时间:
2011-05-20 - 期刊:
- 影响因子:0
- 作者:
Ronald J Buckanovich;R. Berger;A. Sella;B. Sikic;Xiaodong Shen;D. Ramies;David C. Smith;I. Vergote - 通讯作者:
I. Vergote
Ronald J Buckanovich的其他文献
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{{ truncateString('Ronald J Buckanovich', 18)}}的其他基金
Project 3: Hedgehog Inhibition to Enhance Response to ICI Therapy
项目 3:Hedgehog 抑制增强 ICI 治疗反应
- 批准号:
10713054 - 财政年份:2023
- 资助金额:
$ 216.38万 - 项目类别:
Evaluating unique aspects of quiescent ovarian cancer cell biology for therapeutic targets
评估静息卵巢癌细胞生物学的独特方面以寻找治疗靶点
- 批准号:
10750118 - 财政年份:2023
- 资助金额:
$ 216.38万 - 项目类别:
Defining the impact of stromal aging on ovarian cancer initiation
定义基质老化对卵巢癌发生的影响
- 批准号:
10353485 - 财政年份:2021
- 资助金额:
$ 216.38万 - 项目类别:
Defining the impact of stromal aging on ovarian cancer initiation
定义基质老化对卵巢癌发生的影响
- 批准号:
10491889 - 财政年份:2021
- 资助金额:
$ 216.38万 - 项目类别:
Defining the impact of stromal aging on ovarian cancer initiation
定义基质老化对卵巢癌发生的影响
- 批准号:
10659225 - 财政年份:2021
- 资助金额:
$ 216.38万 - 项目类别:
ALDH Inhibition as Modulator of Tumor Immunobiology
ALDH 抑制作为肿瘤免疫生物学的调节剂
- 批准号:
10649413 - 财政年份:2020
- 资助金额:
$ 216.38万 - 项目类别:
ALDH Inhibition as Modulator of Tumor Immunobiology
ALDH 抑制作为肿瘤免疫生物学的调节剂
- 批准号:
10380368 - 财政年份:2020
- 资助金额:
$ 216.38万 - 项目类别:
ALDH Inhibition as Modulator of Tumor Immunobiology
ALDH 抑制作为肿瘤免疫生物学的调节剂
- 批准号:
10524133 - 财政年份:2020
- 资助金额:
$ 216.38万 - 项目类别:
ALDH Inhibition as Modulator of Tumor Immunobiology
ALDH 抑制作为肿瘤免疫生物学的调节剂
- 批准号:
10392913 - 财政年份:2020
- 资助金额:
$ 216.38万 - 项目类别:
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