Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy
整合基因组学和蛋白质相互作用组用于 HPV 头颈癌治疗
基本信息
- 批准号:9982266
- 负责人:
- 金额:$ 77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-15 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-KinaseAddressBasic ScienceCancer EtiologyClinicalClinical TreatmentClinical TrialsDependenceDiseaseERBB3 geneEpidemicEpidemiologyEpidermal Growth Factor ReceptorFamily memberGenital systemGenomicsGrowthHead and Neck CancerHuman PapillomavirusIncidenceIndividualMalignant NeoplasmsMediatingMetastatic/RecurrentMolecularMorbidity - disease rateMutationOperative Surgical ProceduresPIK3CA genePTEN genePathogenesisPatient CarePatientsPositioning AttributePre-Clinical ModelProteinsResearchRoleSignal TransductionSmokerTranslatingTranslational ResearchVaccinationboyscancer therapycervical and anal cancerchemoradiationexperiencefunctional genomicsgirlshead and neck cancer patienthuman interactomeinnovationmultidisciplinarynew therapeutic targetnon-smokernovel strategiesnovel therapeutic interventionpredictive markerprogramssuccess
项目摘要
Project Summary/Abstract
There is an emerging epidemic of head and neck cancer caused by human papillomavirus (HPV) among both
smokers and nonsmokers. While vaccination of boys and girls prior to genital HPV exposure is likely to reduce
HPV+ HNC, the impact of vaccination won’t be realized for decades. In the meantime, HPV+ HNC patients are
treated with disfiguring surgeries and combined chemoradiation approaches, which are associated with
significant short- and long-term morbidities. Individuals with recurrent/metastatic HPV+ HNC generally
succumb to their disease. My research program will apply new approaches in functional genomics and
mapping networks of physical interactions among cancer proteins in relevant and unique HPV+ HNC
preclinical models to translate cancer dependencies in this malignancy into more effective and less toxic
therapies. In this proposal, I build upon our past success in 1) defining key genomic “driver” alterations in HNC;
2) developing novel therapeutic approaches; and 3) translating our discoveries using relevant preclinical
models into clinical treatments for HNC patients. My future research program seeks to 1) define the key
genetic alterations that mediate HPV+ HNC growth in conjunction with determination of the protein interactome
to identify new therapeutic targets; 2) determine the mechanisms of each target and its role in HPV+ HNC; and
3) translate these findings into new treatments for HPV+ HNC. I will begin with the study of targets that have
emerged in our research as relevant in HPV+ HNC such as alterations that activate phosphatidylinositol 3-
kinase (PI3K) signaling including mutation or amplification of PIK3CA, or PTEN loss, and activation of the
EGFR family member HER3. When relevant, I will extend these findings to other HPV+ cancers including
cervical and anal cancers as well as HPV- HNC, which remain lethal. With deep expertise in the molecular
pathogenesis and care of patients with HNC; experience leading multi-disciplinary teams focused on
translational research approaches for this disease and a rich network of basic science and clinical
collaborators, I am uniquely positioned to succeed in the 7 year research plan delineated in this proposal.
项目总结/摘要
有一个新的流行病的头部和颈部癌症引起的人乳头瘤病毒(HPV),
吸烟者和不吸烟者。虽然在生殖器HPV暴露之前接种疫苗的男孩和女孩可能会减少
HPV+ HNC,疫苗接种的影响几十年内都不会实现。HPV+ HNC患者
通过毁容手术和联合放化疗方法治疗,这与
严重的短期和长期发病率。复发性/转移性HPV+ HNC的个体通常
屈服于他们的疾病我的研究计划将应用功能基因组学的新方法,
相关和独特HPV+ HNC中癌蛋白之间物理相互作用的映射网络
临床前模型,将这种恶性肿瘤中的癌症依赖性转化为更有效和毒性更低的
治疗在这个建议中,我建立在我们过去成功的基础上:1)定义HNC中关键的基因组“驱动”改变;
2)开发新的治疗方法;以及3)使用相关的临床前研究成果转化我们的发现
用于HNC患者的临床治疗。我未来的研究计划旨在1)定义关键
介导HPV+ HNC生长的遗传改变以及蛋白质相互作用组的测定
确定新的治疗靶点; 2)确定每个靶点的机制及其在HPV+ HNC中的作用;以及
3)将这些发现转化为HPV+ HNC的新疗法。我将开始研究目标,
在我们的研究中出现了与HPV+ HNC相关的变化,例如激活磷脂酰肌醇3-
在一些实施方案中,本发明涉及一种用于抑制PI 3 K信号传导的方法,包括PIK 3CA的突变或扩增,或PTEN缺失,以及PIK 3CA的激活。
EGFR家族成员HER 3。当相关时,我将把这些发现扩展到其他HPV+癌症,包括
宫颈癌和肛门癌以及HPV-HNC,它们仍然是致命的。在分子生物学领域有着深厚的专业知识
HNC患者的发病机制和护理;领导多学科团队的经验,
这种疾病的转化研究方法和丰富的基础科学和临床网络
合作者,我独特的定位,成功地在7年的研究计划中描绘了这一建议。
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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Jennifer Rubin Grandis其他文献
Retinoic acid normalizes the increased gene transcription rate of TGF–α and EGFR in head and neck cancer cell lines
维甲酸可使头颈癌细胞系中 TGF–α 和 EGFR 基因转录速率增加恢复正常
- DOI:
10.1038/nm0296-237 - 发表时间:
1996-02-01 - 期刊:
- 影响因子:50.000
- 作者:
Jennifer Rubin Grandis;Qing Zeng;David J. Tweardy - 通讯作者:
David J. Tweardy
Phospholipase C-γ1 in tumor progression
- DOI:
10.1023/a:1024088922957 - 发表时间:
2003-07-01 - 期刊:
- 影响因子:3.200
- 作者:
Alan Wells;Jennifer Rubin Grandis - 通讯作者:
Jennifer Rubin Grandis
Jennifer Rubin Grandis的其他文献
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{{ truncateString('Jennifer Rubin Grandis', 18)}}的其他基金
Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy
整合基因组学和蛋白质相互作用组用于 HPV 头颈癌治疗
- 批准号:
10664975 - 财政年份:2018
- 资助金额:
$ 77万 - 项目类别:
Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy
整合基因组学和蛋白质相互作用组用于 HPV 头颈癌治疗
- 批准号:
9764300 - 财政年份:2018
- 资助金额:
$ 77万 - 项目类别:
Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy
整合基因组学和蛋白质相互作用组用于 HPV 头颈癌治疗
- 批准号:
10224700 - 财政年份:2018
- 资助金额:
$ 77万 - 项目类别:
Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy
整合基因组学和蛋白质相互作用组用于 HPV 头颈癌治疗
- 批准号:
10456330 - 财政年份:2018
- 资助金额:
$ 77万 - 项目类别:
GPCR Signaling in SCCHN: Integration with EGFR
SCCHN 中的 GPCR 信号转导:与 EGFR 整合
- 批准号:
8606299 - 财政年份:2014
- 资助金额:
$ 77万 - 项目类别:
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