Predictive biomarker development in lung cancer: ROS1 chromosomal rearrangements

肺癌预测生物标志物的发展：ROS1染色体重排

• 批准号: 8298508
• 负责人: Anthony John Iafrate
• 金额: $ 19.25万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-07 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8298508
• 关键词: ALK gene; Adenocarcinoma; Adoption; Age; Archives; BRAF gene; Biological Assay; Biological Markers; Brain Neoplasms; Cancer Diagnostics; Cancer Patient; Cell Line; Chromosomal Rearrangement; Clinical; Clinical Trials; Community Clinical Oncology Program; DNA Sequence Rearrangement; Data; Development; Diagnosis; Diagnostic; ERBB2 gene; Enrollment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Fluorescent in Situ Hybridization; Future; General Hospitals; Genetic; Genotype; Glioblastoma; Home environment; Imatinib; Immunohistochemistry; In Vitro; Individual; Institution; Knowledge; Laboratories; Learning; Lung Adenocarcinoma; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of lung; Massachusetts; Methods; Molecular Analysis; Mutation; Non-Small-Cell Lung Carcinoma; Pathology; Patient Care; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Phase III Clinical Trials; Phosphotransferases; Population; ROS1 gene; Receptor Tyrosine Kinase Gene; Relative (related person); Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Somatic Mutation; Specimen; Staging; Standardization; Technical Expertise; Technology; Testing; Therapeutic; Time; Trastuzumab; Tumor Tissue; Work; base; bcr-abl Fusion Proteins; beneficiary; cancer diagnosis; cancer genetics; cancer therapy; clinical application; cohort; cost; cost effective; design; drug development; experience; genetic profiling; improved; inhibitor/antagonist; interest; kinase inhibitor; malignant breast neoplasm; melanoma; model development; mutant; next generation; non-smoker; novel; open source; patient population; prospective; research study; response; small molecule; tumor

DESCRIPTION (provided by applicant): Over the last two years, patients diagnosed with cancer at the Massachusetts General Hospital (MGH) have been the beneficiaries of the successful implementation of a clinical, high-throughput tumor genotyping platform. This has helped transform cancer diagnosis from a purely morphologic assessment to a prospective molecular analysis. Knowledge of the mutational status of an individual tumor means that clinicians can decide on the treatment that is best for that patient. Furthermore, the matching of experimental therapeutics to the patients most likely to respond accelerates the adoption novel therapies and advances patient care. The overall objective of this proposal is to design and develop a robust clinical assay to detect ROS1 rearrangements in lung cancer. Building on the lessons learned from our successful implementation of diagnostics to detect chromosomal rearrangements involving the ALK gene, we will identify, test, validate, and implement the optimal ROS1 assay platform. We will test the feasibility of using a variety of assay platforms including fluorescence in situ hybridization, immunohistochemistry and PCR for clinical application. This objective will be achieved in two aims: (1) To establish assays for assessing ROS1 rearrangements in non-small cell lung carcinoma and (2) to perform ROS1 assay comparisons of sensitivity and specificity in a larger NSCLC cohort. This proposal will allow the timely implementation of novel ROS1 diagnostics that will enable the efficient identification of a subset of lung cancer patients that may benefit from new small molecule inhibitors that target the ROS1 kinase. This project will serve as a model for development and clinical implementation of diagnostics for the benefit of patients, and will be used to disseminate knowledge and expertise to the academic field of clinical lung cancer diagnostics in general.

描述（由申请人提供）：在过去的两年中，马萨诸塞州总医院（MGH）诊断为癌症的患者已经成为临床高通量肿瘤基因分型平台成功实施的受益者。这有助于将癌症诊断从纯粹的形态学评估转变为前瞻性的分子分析。了解单个肿瘤的突变状态意味着临床医生可以决定对该患者最好的治疗方案。此外，实验疗法与最有可能产生反应的患者的匹配加速了新疗法的采用，并提高了患者的护理水平。本提案的总体目标是设计和开发一种强大的临床检测方法来检测肺癌中的ROS1重排。基于我们成功实施诊断以检测涉及ALK基因的染色体重排的经验教训，我们将确定、测试、验证和实施最佳的ROS1检测平台。我们将测试使用多种检测平台的可行性，包括荧光原位杂交，免疫组织化学和PCR用于临床应用。这一目标将在两个方面实现：(1)建立评估ROS1重排在非小细胞肺癌中的检测方法；(2)在更大的非小细胞肺癌队列中进行ROS1检测的敏感性和特异性比较。该建议将允许及时实施新的ROS1诊断方法，从而能够有效地识别可能受益于靶向ROS1激酶的新小分子抑制剂的肺癌患者亚群。该项目将作为诊断开发和临床实施的典范，造福患者，并将用于向临床肺癌诊断的学术领域传播知识和专业知识。