Discovery and therapeutic targeting of biological determinants of lung cancer health disparities

肺癌健康差异的生物决定因素的发现和治疗靶向

基本信息

  • 批准号:
    10684394
  • 负责人:
  • 金额:
    $ 37.38万
  • 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:
    2020-05-15 至 2026-01-31
  • 项目状态:
    未结题

项目摘要

Lung cancer is the leading cause of all cancer deaths in the U.S. and worldwide. Lung cancer risk and survival are heterogeneously distributed among U.S. populations. African-American men have a higher incidence of and poorer survival from lung cancer than European-American men, even after adjusting for smoking and socioeconomic factors. The tumor-specific biological factors responsible for the racial differences are not yet understood. The goal of this project is to define the mechanisms by which the JAK/STAT3 pathway operates as a key biological contributor of racial health disparities in non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), the most common histological subtype of lung cancer. Our preliminary data suggest that LUADs from African Americans are more likely than LUADs from European Americans to have JAK/STAT3 pathway mutations that directly induce persistent activation of Signal Transducer and Activator of Transcription-3 (STAT3). STAT3 is an oncogenic transcription factor that is hyperactivated in many cancers. It drives expression of genes that regulate anti-apoptotic responses, angiogenesis, cell proliferation, tumor progression, and therapeutic resistance. The premise of this application is that the JAK/STAT3 signaling axis is inappropriately activated by mutations that are more common in LUAD from African Americans than European Americans, and that therapeutic intervention will be of clinical benefit to a molecular subset of patients with LUAD. Given that the molecular subset is more common in African Americans, research on this topic could help narrow the gap in health disparities. Aim 1 will characterize the molecular profiles in LUAD from African Americans and European Americans focusing on JAK/STAT3 and impact on racial differences. In Aim 2, we will utilize CRISPR-mediated genome editing on patient-derived models of cancer from LUAD tumors from African Americans, and other models, to test the hypothesis that aberrant STAT3 activation results from specific mutations in the JAK/STAT3 pathway, and that the mutations drive LUAD development and tumor progression. In Aim 3, utilizing patient-derived LUAD xenografts primarily from African-American patients, we will test the hypothesis that the JAK/STAT3 pathway mutations we identified can serve as predictive biomarkers for effective antitumor response to STAT3 blockade in LUAD, and we will further clarify novel biomarkers of effective tumor response. At the conclusion of this project, we will have uncovered a novel set of biological determinants of NSCLC health disparities. If the results of the study support our hypothesis, they will provide a path to future clinical trials that may improve the clinical outcome of LUAD patients and help reduce lung cancer health disparities.
肺癌是美国和全世界所有癌症死亡的主要原因。肺癌的风险和生存

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 }}

Sharon R. Pine其他文献

BRAF fusion as a novel mechanism of acquired resistance to vemurafenib in BRAF V 600 E mutant 3 melanoma 4 5
BRAF 融合作为 BRAF V 600 E 突变体 3 黑色素瘤中对维莫非尼获得性耐药的新机制 4 5
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    A. Kulkarni;Husam Al;Srilatha Simhadri;K. Hirshfield;Suzie Chen;Sharon R. Pine;C. Jeyamohan;Levi Sokol;Siraj M. Ali;M. L. Teo;E. White;L. Rodriguez;J. Mehnert;S. Ganesan
  • 通讯作者:
    S. Ganesan
Lymphoproliferative clonal origin of AIDS-related non-Hodgkin's lymphoma
艾滋病相关非霍奇金淋巴瘤的淋巴增殖性克隆起源
  • DOI:
    10.1080/10428190601173109
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    H. Sabaawy;C. Sandoval;Qianxu Guo;Changhong Yin;A. Kulangara;Jooyun Lee;Gary Wormser;S. Jayabose;Sharon R. Pine
  • 通讯作者:
    Sharon R. Pine
Abstract 1957: Negative regulation of Sox9 by glycogen synthase kinase 3 beta phosphorylation and SCFFbw7-dependent ubiquitination in cancer
摘要 1957 年:癌症中糖原合酶激酶 3 β 磷酸化和 SCFFbw7 依赖性泛素化对 Sox9 的负调控
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Xuehui Hong;Wenyu Liu;H. Inuzuka;Lianxin Liu;Sharon R. Pine
  • 通讯作者:
    Sharon R. Pine
Down syndrome Incidence and clinical implications of GATA1 mutations in newborns with
唐氏综合症新生儿 GATA1 突变的发病率和临床意义
  • DOI:
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    0
  • 作者:
    C. Sandoval;Sharon R. Pine;Qianxu Guo;Changhong Yin;S. Jayabose;C. Druschel
  • 通讯作者:
    C. Druschel
GATA1 Mutations in Newborns with Down Syndrome.
患有唐氏综合症的新生儿中的 GATA1 突变。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    C. Sandoval;Sharon R. Pine;C. Druschel;S. Jayabose;Qianxu Guo;Changhong Yin
  • 通讯作者:
    Changhong Yin

Sharon R. Pine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('Sharon R. Pine', 18)}}的其他基金

Discovery and therapeutic targeting of biological determinants of lung cancer health disparities
肺癌健康差异的生物决定因素的发现和治疗靶向
  • 批准号:
    10385769
  • 财政年份:
    2020
  • 资助金额:
    $ 37.38万
  • 项目类别:
Discovery and therapeutic targeting of biological determinants of lung cancer health disparities
肺癌健康差异的生物决定因素的发现和治疗靶向
  • 批准号:
    10158464
  • 财政年份:
    2020
  • 资助金额:
    $ 37.38万
  • 项目类别:
Sox9 signaling in lung adenocarcinoma
肺腺癌中的 Sox9 信号传导
  • 批准号:
    8798984
  • 财政年份:
    2014
  • 资助金额:
    $ 37.38万
  • 项目类别:
Sox9 signaling in lung adenocarcinoma
肺腺癌中的 Sox9 信号传导
  • 批准号:
    9479728
  • 财政年份:
    2014
  • 资助金额:
    $ 37.38万
  • 项目类别:
Asymmetric Cell Division and Notch Signaling in Lung Cancer Stem Cells
肺癌干细胞中的不对称细胞分裂和Notch信号传导
  • 批准号:
    7892613
  • 财政年份:
    2011
  • 资助金额:
    $ 37.38万
  • 项目类别:
Asymmetric Cell Division and Notch Signaling in Lung Cancer Stem Cells
肺癌干细胞中的不对称细胞分裂和Notch信号传导
  • 批准号:
    8250342
  • 财政年份:
    2011
  • 资助金额:
    $ 37.38万
  • 项目类别:
Asymmetric Cell Division and Notch Signaling in Lung Cancer Stem Cells
肺癌干细胞中的不对称细胞分裂和Notch信号传导
  • 批准号:
    8461918
  • 财政年份:
    2011
  • 资助金额:
    $ 37.38万
  • 项目类别:
Asymmetric Cell Division and Notch Signaling in Lung Cancer Stem Cells
肺癌干细胞中的不对称细胞分裂和Notch信号传导
  • 批准号:
    8700862
  • 财政年份:
    2011
  • 资助金额:
    $ 37.38万
  • 项目类别:

相似海外基金

Broadening Participation Research: Understanding faculty attitudes, competency, and perceptions of providing career advising to African American STEM students at HBCUs
扩大参与研究:了解教师对 HBCU 的非裔美国 STEM 学生提供职业建议的态度、能力和看法
  • 批准号:
    2306671
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Continuing Grant
Cognitive Behavioral Faith-based Depression Intervention For African American Adults (CB-FAITH): An Effectiveness And Implementation Trial
非裔美国成年人基于认知行为信仰的抑郁干预 (CB-FAITH):有效性和实施试验
  • 批准号:
    10714464
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
DELINEATING THE ROLE OF THE HOMOCYSTEINE-FOLATE-THYMIDYLATE SYNTHASE AXIS AND URACIL ACCUMULATION IN AFRICAN AMERICAN PROSTATE TUMORS
描述同型半胱氨酸-叶酸-胸苷酸合成酶轴和尿嘧啶积累在非裔美国人前列腺肿瘤中的作用
  • 批准号:
    10723833
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
Preventing Firearm Suicide Deaths Among Black/African American Adults
防止黑人/非裔美国成年人因枪支自杀死亡
  • 批准号:
    10811498
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
Exploring PTSD Symptoms, Barriers and Facilitators to Mindfulness-based Stress Reduction for Justice-Involved Black/African American Female Adolescents and Parents/Caregivers
探索创伤后应激障碍 (PTSD) 症状、障碍和促进因素,为涉及正义的黑人/非裔美国女性青少年和父母/照顾者进行基于正念的减压
  • 批准号:
    10593806
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
BCSER - PVEST: A Dynamic Framework for Investigating STEM Interest, Attitude and Identity Among African American Middle School Students
BCSER - PVEST:调查非裔美国中学生 STEM 兴趣、态度和身份的动态框架
  • 批准号:
    2327055
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Standard Grant
Making the Connection: Understanding the dynamic social connections impacting type 2 diabetes management among Black/African American men
建立联系:了解影响黑人/非裔美国男性 2 型糖尿病管理的动态社会联系
  • 批准号:
    10782674
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
Building a Community-Based Mental Health Literacy Intervention for African American Young Adults
为非裔美国年轻人建立基于社区的心理健康素养干预措施
  • 批准号:
    10738855
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
African American Literature in "post" Post-Racial America
“后”后种族美国中的非裔美国文学
  • 批准号:
    23K00376
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Neurovascular Control of Renal Blood Flow During Exercise in African American Adults
非裔美国成年人运动期间肾血流的神经血管控制
  • 批准号:
    10653381
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了