Proteogenomic Predictors of Recurrence in Non-small Cell Lung Cancer

非小细胞肺癌复发的蛋白质基因组预测因素

• 批准号: 10459716
• 负责人: STEVEN A CARR
• 金额: $ 108.43万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10459716
• 关键词: Adenocarcinoma Cell; Adjuvant; Assessment tool; Biological Assay; Biological Markers; Cancer Etiology; Center for Translational Science Activities; Cessation of life; Characteristics; Clinical; Clinical Trials; Coupled; Data; Data Analyses; Enrollment; Epidermal Growth Factor Receptor; Erlotinib; Excision; Funding; Genome; Genomics; Human; Institutes; Intervention Trial; Lung Adenocarcinoma; Machine Learning; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Mass Spectrum Analysis; Multicenter Studies; Mutation; National Cancer Institute; National Clinical Trials Network; Nivolumab; Nodal; Non-Small-Cell Lung Carcinoma; Nonmetastatic; Operative Surgical Procedures; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Peptides; Phosphorylation; Platinum; Post-Translational Protein Processing; Postoperative Period; Prognostic Factor; Prognostic Marker; Protein Tyrosine Kinase; Proteins; Proteome; Proteomics; Randomized; Recurrence; Relapse; Research Personnel; Resectable; Resected; Risk; Risk Factors; Role; Sampling; Specimen; Squamous Cell Lung Carcinoma; Systemic Therapy; Testing; Therapeutic Trials; Tissue Sample; Training; Translating; Universities; Validation; Washington; anaplastic lymphoma kinase; assay development; base; biomarker identification; cancer cell; cancer genome; chemotherapy; cohort; crizotinib; exome; genomic data; immune checkpoint blockade; improved; improved outcome; inhibitor; lymphatic Invasion; medical schools; molecular targeted therapies; mutant; outcome prediction; patient subsets; predictive marker; prognostic; prognostic model; programmed cell death ligand 1; programmed cell death protein 1; proteogenomics; randomized trial; relapse prediction; relapse risk; screening; standard of care; support network; transcriptome; transcriptomics; trial comparing; tumor; whole genome; working group

PROJECT SUMMARY/ABSTARCT Lung cancer is a leading cause of cancer-related death globally. Nearly a third of patients with non-small cell lung cancer (NSCLC) present with potentially resectable early-stage NSCLC. Despite complete resection, approximately 50% of patients with stage II and III NSCLC recur and die from metastatic NSCLC. There are no reliable biomarkers to predict poor outcomes in early-stage NSCLC. Molecularly targeted therapies and immune checkpoint blockade targeting programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) have significantly improved the outcomes of patients with metastatic NSCLC, and these agents are now undergoing clinical trials in early-stage lung cancer following standard therapy. The National Cancer Institute (NCI) has launched an ambitious multicenter study, the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing (ALCHEMIST), to screen nearly 8000 patients with completely resected NSCLC to identify those with activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) and rearrangements in anaplastic lymphoma kinase (ALK) to investigate the role of erlotinib and crizotinib, respectively. Those with tumors lacking EGFR mutation or ALK rearrangement were offered participation in a randomized trial comparing nivolumab, an inhibitor of PD-1 to observation. The ALCHEMIST Genomics Working Group is planning to study the tumor whole genomes, exomes, and transcriptomes from nearly 2000 patients who did not participate in the intervention trials (ALCHEMIST Screening Study) and all those enrolled in the three ALCHEMIST therapeutic trials. This suite of trials with data generated using genomic analyses provides a unique opportunity to explore the role of the cancer proteome in predicting outcomes in patients with resected NSCLC. We propose a Proteogenomic Translational Research Center (PTRC) to study the proteogenomic alterations in resected early-stage NSCLC co-led by the Washington University School of Medicine (WUSM) and the Broad Institute along with investigators affiliated with the NCI-funded National Clinical Trials Network (NCTN) supporting the ALCHEMIST suite of clinical trials. Our overarching objective is to apply mass spectrometry-based global and targeted proteomic analyses to patient-derived resected tumor material to improve upon the predictive biomarkers using somatic cancer genome and transcriptome and clinical characteristics. These discoveries will be translated into targeted assays to predict recurrence following therapy. Since the ALCHEMIST Crizotinib study is still ongoing and has enrolled relatively fewer patients compared to other studies, we will not include those samples in this proposal. The three aims of this project are to develop prognostic assessment tools to predict relapse in patients with resected NSCLC treated with standard platinum doublet chemotherapy (aim 1), standard platinum doublet chemotherapy and nivolumab (aim 2), and standard platinum doublet chemotherapy and erlotinib (aim 3) using proteogenomics.

项目总结/ ABSTARCT