P-1: Molecular Signatures for Individualizing Lung Cancer Therapy

P-1：个体化肺癌治疗的分子特征

• 批准号: 8731332
• 负责人: JOHN D. MINNA
• 金额: $ 15.66万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-12 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731332
• 关键词: Antineoplastic Agents; Biological Assay; Biological Markers; Cancer Patient; Cancer cell line; Cell Line; Clinic; Clinical; Drug Combinations; Drug Targeting; Effectiveness; Exhibits; Goals; Histologic; Human; In Vitro; Individual; Inhibitory Concentration 50; Lung; Malignant neoplasm of lung; Measures; Messenger RNA; Modeling; Molecular Profiling; Non-Small-Cell Lung Carcinoma; Patients; Pharmaceutical Preparations; Phase; Phenotype; Pre-Clinical Model; Protein Array; Proteins; Relative (related person); Resistance; Sampling; Specimen; Testing; Texas; Therapeutic Agents; Tumor Cell Line; Universities; Xenograft procedure; base; cancer cell; cancer therapy; chemotherapy; drug sensitivity; effective therapy; improved; in vivo; lung small cell carcinoma; lung xenograft; mRNA Expression; pre-clinical; pre-clinical therapy; protein expression; response; subcutaneous; tissue culture; tumor; tumor xenograft

Non-small cell lung cancers (NSCLCs) from patients exhibit large differences in sensitivity or resistance to chemotherapy and targeted drugs. We hypothesize that these differences will be reflected in tumor mRNA and protein signatures prior to treatment, and that these signatures can be used to improve the effectiveness of therapy. The eventual goal to develop and use such signatures to determine the best available treatment for that individual. To move towards this goal, however, there is a critical need for preclinical models to develop such signatures and test new therapies. This project proposes to use a large panel of NSCLC cell lines and xenografts to systematically measure preclinical therapy response phenotypes, define associated mRNA and protein biomarker signatures of these responses, and then validate these in other cell lines, xenografts, and patient tumor specimens. We will also identify mRNA and protein biomarkers in patient specimens and test them in the preclinical models, eventually resulting in validated biomarkers for response prediction in patients and validated preclinical models. Specific Aims are: Aim 1) To measure quantitative drug sensitivity/resistance phenotypes in a large panel (-100) of human NSCLC cell lines and xenografts (~50), including xenografts made directly from patient tumors without intervening culture, and compare in vitro drug response phenotypes with those of orthotopic (lung) xenografts; Aim 2) To identify microarray mRNA and reverse phase protein array (RPPA)-based expression signatures of response to therapeutic agents in NSCLC lines; using these signatures we will predict drug responses in a new

来自患者的非小细胞肺癌（nsclc）在对