Integrative Oncogenomics of Multiple Myeloma

多发性骨髓瘤的综合肿瘤基因组学

• 批准号: 8326575
• 负责人: Nikhil C. Munshi
• 金额: $ 199.93万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326575
• 关键词: Address; Affect; Automobile Driving; Awareness; Basic Science; Behavior; Bioinformatics; Biological; Biological Markers; Bone Marrow; Bone Marrow Cells; Bortezomib; Cell Communication; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Combined Modality Therapy; Communication; DNA; DNA Sequencing Facility; Development; Disease; Disease Outcome; Disease Progression; Dose; Drug resistance; Enrollment; Event; Evolution; Genetic; Genome; Genomic Instability; Genomics; Goals; Growth; High-Dose Chemotherapy with Autologous Stem Cell Transplant; In Vitro; In complete remission; Individual; Institutes; International; Investigation; Lead; Lesion; Molecular; Molecular Genetics; Multiple Myeloma; Newly Diagnosed; Outcome; Pathogenesis; Pathway interactions; Patients; Prevalence; Refractory; Relapse; Research; Research Personnel; Role; Sampling; Stromal Cells; Subgroup; Technology; Therapeutic; Therapeutic Agents; Tissues; Translating; Transplantation; United States; Validation; bench to bedside; cancer genomics; cell growth; clinically relevant; clinically significant; collaborative trial; cytotoxicity; drug discovery; genetic analysis; genome sequencing; improved; in vivo; in vivo Model; lenalidomide; malignant phenotype; neoplastic cell; new therapeutic target; next generation; novel; outcome forecast; pre-clinical; preclinical study; prevent; prognostic; programs; response; therapy development

Our myeloma research group, which has developed number of new targets and novel therapies (DFCI), will partner with the world leaders in cooperative clinical and transplantation trials in MM (IFM) to pursue collaborative translational investigation. We will couple combination novel therapies with high dose therapy and transplantation and then delineate genomic and molecular correlates of clinical and biological outcomes. Project 1 will focus on defining the durability of responses to novel combination therapy on the one hand, and the additional value of high dose therapy on the other, by enrolling 1000 newly diagnosed patients between IFM and DFCI. This trial will provide 1000 samples from newly diagnosed and uniformly treated patients to comprehensively characterize the MM genome and epigenome, to define molecular events driving development and progression of MM (Project 2), as well as to identify novel therapeutic targets (Project 3), biomarkers, and preventative strategies (Project 4). In these collaborative studies the Sanger Institute in UK, with whole genome sequencing capabilities, along with research teams from DFCI and IFM, will perform molecular genetic analysis of patient samples and delineate patient subgroups most likely to respond and achieve prolonged survival (Projects 2 and 4). The clinically relevant novel targets identified using these high throughput genomic technologies will be validated and novel targeted therapies developed in Project 3. Project 4 will further analyze evolution of genomic changes at relapse and their clinical significance, as well as devise strategies to prevent genomic instability. These 4 projects will be supported by Administrative and Communication Core (A), Clinical and Tissue Core (B); Genomics Core (C); Genomic Sequencing Core (0), and Biostatistical and Bioinformatics Core (E). This unique collaborative effort will define a new treatment paradigm for this presently incurable disease.

我们的骨髓瘤研究小组已经开发了许多新靶点和新疗法 (DFCI)，将与多发性骨髓瘤合作临床和移植试验 (IFM) 的世界领先者合作，开展合作转化研究。我们将联合新疗法与高剂量疗法和移植相结合，然后描绘临床和生物学结果的基因组和分子相关性。项目 1 将重点关注通过在 IFM 和 DFCI 之间招募 1000 名新诊断患者，一方面确定新型联合疗法反应的持久性，另一方面确定高剂量疗法的附加价值。该试验将提供来自新诊断和统一治疗的患者的 1000 个样本，以全面表征 MM 基因组和表观基因组，定义驱动 MM 发生和进展的分子事件（项目 2），并确定新的治疗靶点（项目 3）、生物标志物和预防策略（项目 4）。在这些合作研究中，拥有全基因组测序能力的英国桑格研究所将与 DFCI 和 IFM 的研究团队一起，对患者样本进行分子遗传学分析，并确定最有可能做出反应并实现延长生存期的患者亚组（项目 2 和 4）。使用这些高通量基因组技术确定的临床相关新靶标将在项目 3 中得到验证并开发新的靶向疗法。项目 4 将进一步分析复发时基因组变化的演变及其临床意义，并制定预防基因组不稳定的策略。这4个项目将得到行政和沟通核心（A）、临床和组织核心（B）的支持；基因组学核心（C）；基因组测序核心 (0) 和生物统计和生物信息学核心 (E)。这种独特的合作努力将为这种目前无法治愈的疾病定义一种新的治疗模式。