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Integrated Molecular, Cellular, and Imaging Characterization of NLST detected lung cancer

NLST 检测肺癌的综合分子、细胞和成像特征

基本信息

批准号：
10415430
负责人：
DENISE R. ABERLE
金额：
$ 15.6万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2021-09-22 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10415430
关键词：
Address Aggressive Clinical Course Aggressive behavior Alleles Behavior Biological Cells Clinical Clinical Management DNA Development Effectiveness Funding Genes Genomics Goals Health Policy Image Immune Immunofluorescence Immunologic Individual Indolent Lung Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Medicare Modeling Molecular Mutation Outcome Patients Phenotype Preventive service Research Resected Role Sampling Sea Smoker Somatic Mutation Specimen Third-Party Payer Thoracic Radiography Tissue Microarray Tissue Stains Tissues Tumor Biology X-Ray Computed Tomography base biobank cancer diagnosis cellular imaging clinical decision-making clinical heterogeneity computed tomography screening exome sequencing genomic data high risk low dose computed tomography lung cancer screening mortality new therapeutic target novel personalized management precision medicine screening tumor tumor-immune system interactions

项目摘要

PROJECT SUMMARY/ABSTRACT The landmark NLST demonstrated a 20% mortality reduction in lung cancer in individuals who underwent low dose computed tomography (LDCT) screening relative to plain chest radiography. The results of the NLST have resulted in a sea change in US health policy, such that third party payers and Medicare now provide LDCT screening as a preventive service benefit in eligible, high risk smokers. Understanding the factors underlying tumor indolence or aggression that result in heterogeneous clinical outcomes, may facilitate clinical decision making in the context of lung cancer screening and thereby greatly increase its effectiveness. We hypothesize that the mutational landscape of screen-detected lung cancers is an important contributor to their indolence or aggressiveness. To address this hypothesis we will take advantage of the comprehensively annotated NLST biorepository. Whole exome sequencing (WES) of the previously collected NLST samples will be performed to determine the genomic features that distinguish between screen-detected indolent and aggressive lung tumors that result in heterogeneous clinical outcomes. Samples from 110 patients with aggressive cancers and 494 with indolent cancers along with matching reference tissues will be assessed. By utilizing WES, we will be able to identify the impact of genes not previously associated with lung cancer as well as novel alleles of genes with known roles in lung cancer. This will be the first comprehensive genomic characterization of aggressive and indolent lung cancers diagnosed in the course of a lung cancer screening trial. The detailed genomic and imaging-based characterization of screen-detected tumors will ultimately impact clinical management of those cancers. Through separate funding, we will also integrate the genomic data obtained through this research with the tumor immune microenvironment (as characterized by multiplex immunofluorescence analysis of the same specimens) and CT imaging features to build integrated, multiparametric models of tumor biology that can be used to predict the biological behavior of lung cancers in the screening setting.

项目总结/文摘

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（2）

Drug Development for Metastasis Prevention.

预防转移的药物开发。

DOI：
10.1615/critrevoncog.v20.i5-6.150
发表时间：
2015
期刊：
Critical reviews in oncogenesis
影响因子：
0
作者：
Fontebasso Y;Dubinett SM
通讯作者：
Dubinett SM

CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.

DOI：
10.1186/s13059-017-1191-5
发表时间：
2017-03-24
期刊：
Genome biology
影响因子：
12.3
作者：
Kang S;Li Q;Chen Q;Zhou Y;Park S;Lee G;Grimes B;Krysan K;Yu M;Wang W;Alber F;Sun F;Dubinett SM;Li W;Zhou XJ
通讯作者：
Zhou XJ

Immunosurveillance and Regression in the Context of Squamous Pulmonary Premalignancy.

DOI：
10.1158/2159-8290.cd-20-1087
发表时间：
2020-10
期刊：
Cancer discovery
影响因子：
28.2
作者：
Krysan K;Tran LM;Dubinett SM
通讯作者：
Dubinett SM

Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.

DOI：
10.1016/j.ctarc.2021.100486
发表时间：
2021
期刊：
Cancer treatment and research communications
影响因子：
0
作者：
Burks EJ;Zhang J;Sullivan TB;Shi X;Sands JM;Regis SM;McKee BJ;McKee AB;Zhang S;Liu H;Liu G;Spira A;Beane J;Lenburg ME;Rieger-Christ KM
通讯作者：
Rieger-Christ KM

Understanding the mechanisms of immune-evasion by lung cancer in the context of chronic inflammation in emphysema.

了解肺气肿慢性炎症背景下肺癌免疫逃避的机制。