Improving Treatment Algorithms for Veterans with Oropharyngeal Cancer
改善口咽癌退伍军人的治疗算法
基本信息
- 批准号:10152351
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAlgorithmsAmerican Joint Committee on CancerAreaBiologicalBiometryCD8B1 geneCellsCellular StructuresChronicClinicalClinical TrialsComplexDataDiagnosisDiseaseDoseEnrollmentEnvironmentEpidemiologyEtiologyEvaluationExposure toGene Expression ProfilingGeneral PopulationHuman CharacteristicsHuman PapillomavirusImmuneImmune checkpoint inhibitorImmune responseImmunocompetentImmunohistochemistryImmunomodulatorsIncidenceInflammatory ResponseLightLinkLymphocyteLymphocytic InfiltrateMalignant NeoplasmsManualsMedical centerMentorshipMolecularMyelogenousMyeloid CellsMyeloid-derived suppressor cellsNormal tissue morphologyOncogenic VirusesOropharyngeal Squamous Cell CarcinomaOutcomePatientsPlayPopulationPrincipal InvestigatorRecording of previous eventsRecurrenceRefractoryRegimenRegulatory T-LymphocyteResearchResearch PersonnelRoleSecondary toSelection for TreatmentsSiteSmokerSmokingSmoking HistorySoft PalateStagingSurvival RateT-LymphocyteTobaccoTonsilToxic effectTraining ActivityTreatment FailureTreatment ProtocolsUnresectableUp-RegulationVeteransVeterans Health AdministrationWorkanticancer researchbasecancer therapychemoradiationclinically relevantcohortconventional therapydesigneffective therapyexperienceexperimental studyfollow-uphuman modelimmunomodulatory strategyimmunomodulatory therapiesimprovedmalignant oropharynx neoplasmmeetingsmilitary veteranmouse modelnovelonline courseoptimal treatmentspatient populationstandard caretherapy resistanttobacco exposuretongue roottreatment effecttreatment responsetumortumor immunologytumor-immune system interactions
项目摘要
Oropharyngeal cancer is rapidly increasing in incidence in the veteran population, fueled
largely by exposure to the human papilloma virus (HPV). Although survival for oropharyngeal
squamous cell carcinoma associated with the human papilloma virus (HPV+OPSCC) is excellent
in the general population, it remains dismal in the veteran population, with nearly 1 in 2 patients
dying of their disease within 5 years of diagnosis. This disproportionally poor survival is thought
to be driven in part by tumors which are less responsive to chemo-radiation treatment regimens.
Preliminary data from our group and others suggests this decreased treatment response may be
in part driven by tobacco exposure, which is extremely prevalent among Veterans with
HPV+OPSCC. The hypothesized mechanism of action is a tobacco induced, immunosuppressive
environment which inhibits the normal anti-tumor activity of lymphocytes and other immune cells
during cancer treatment.
In the current proposal, we will first characterize and quantify the relative effect of tobacco
exposure on survival in Veterans with HPV+OPSCC (Aim 1). This is critical in light of the newly
implemented 8th Edition of the AJCC Staging Manual which dramatically down-stages OPSCC
based on HPV status (HPV associated vs non-HPV associated), but does not consider the
potentially critical impact of tobacco exposure on survival. Given the widespread, and extensive
tobacco exposure we and others have demonstrated in Veterans with OPSCC, this represents an
important clinical and translational first step in potentially improving survival for Veterans with this
disease.
We will then characterize the Th1 T-lymphocyte and myeloid derived suppressor cell
(MDSC) components of the tumor immune microenvironment (TIME) in HPV+OPSCC tumors as
a function of tobacco exposure (Aim 2). This will allow us to provide support for our mechanistic
hypothesis and to define the relationship between tobacco exposure and changes in the TIME of
HPV+OPSCC. Finally, we will compare the TIME characteristics of HPV+OPSCC tumors which
fail to respond to conventional chemo-radiation treatment regimens to the TIME of HPV+OPSCC
tumors which do respond to treatment, in order to define an immune signature associated with
treatment resistance in this disease site (Aim 3). Together, these experiments will allow us to: 1)
define a clinically relevant effect size for tobacco exposure vis a vis HPV+OPSCC survival and 2)
begin to define a mechanistic link between tobacco exposure and TIME dependent treatment
response. Successful completion of the proposed research will allow us to more appropriately
prognosticate survival in Veterans with HPV+OPSCC, identify patients which may be candidates
for treatment escalation using immunomodulatory agents (i.e. checkpoint inhibitors) and patients
which should not be enrolled in clinical trials aimed at de-escalation of chemo-radiation regimens
in order to decrease normal tissue toxicity.
In parallel with the proposed research, the Principal Investigator will engage in training
activities designed to provide increased facility and expertise in the areas of Epidemiology and
Biostatistics as well as Tumor Immunology, through a combination of formal and online course
work, participation in institutional, local and national meetings and direct interactions with a
Mentorship Committee with appropriate expertise in these 3 areas of cancer research.
口咽癌在退伍军人中的发病率正在迅速增加
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
VLAD C SANDULACHE其他文献
VLAD C SANDULACHE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('VLAD C SANDULACHE', 18)}}的其他基金
Metabolic adaptation enables cisplatin resistance and inhibits tumor immunity
代谢适应使顺铂耐药并抑制肿瘤免疫
- 批准号:
10942977 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Metabolic adaptation enables cisplatin resistance and inhibits tumor immunity
代谢适应使顺铂耐药并抑制肿瘤免疫
- 批准号:
10707169 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Metabolic adaptation enables cisplatin resistance and inhibits tumor immunity
代谢适应使顺铂耐药并抑制肿瘤免疫
- 批准号:
10518177 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Improving Treatment Algorithms for Veterans with Oropharyngeal Cancer
改善口咽癌退伍军人的治疗算法
- 批准号:
10425236 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Overcoming cisplatin resistance by targeting fatty acid metabolism
通过靶向脂肪酸代谢克服顺铂耐药性
- 批准号:
9980866 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Overcoming cisplatin resistance by targeting fatty acid metabolism
通过靶向脂肪酸代谢克服顺铂耐药性
- 批准号:
9795719 - 财政年份:2019
- 资助金额:
-- - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Studentship