Gene expression profiling and pathway targeted therapy in peripheral T-cell

外周T细胞的基因表达谱和通路靶向治疗

• 批准号: 7715220
• 负责人: Wing C. Chan
• 金额: $ 10.3万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715220
• 关键词: B-Cell Lymphomas; Behavior; Cancer Center; Case Study; Classification; Clinical; Clinical Research; Clinical Trials; Data; Development; Diagnosis; Disease; Doctor of Medicine; Environment; Event; Funding; Future; Gene Expression; Gene Expression Profiling; Grant; Immunoblastic Lymphadenopathy; Immunosuppression; Immunosuppressive Agents; Instruction; Investigation; Lead; Lymphoma; Malignant Neoplasms; Medical center; Molecular; Molecular Profiling; Natural Killer Cells; Oncogenic; Outcome; Pathway interactions; Patients; Peripheral; Phase; Phase II Clinical Trials; Population; Relapse; Reproduction spores; Resources; Role; Series; Study models; Subgroup; T-Cell Lymphoma; T-Lymphocyte; Toxic effect; Treatment Protocols; Tumor Cell Line; Validation; Virus; base; chemotherapy; experience; host neoplasm interaction; improved; infected B cell; inhibitor/antagonist; multicatalytic endopeptidase complex; neoplastic; neoplastic cell; novel; novel therapeutic intervention; response; therapeutic target; tumor; tumorigenesis

Peripheral T-cell lymphoma (PTCL) is an uncommon lymphoma that is often challenging to diagnose and classify. Most patients also have poor survival with standard mulfiagent chemotherapy and new, more effecfive therapeufic approaches are necessary to improve patient outcome. Our experience in using gene expression proflling (GEP) to study B-cell lymphomas indicates that this approach is very promising in improving classificafion, construcfing molecular based prognosticators and detecfing biologically significant pathways that may be targeted for treatment. We hypothesized that GEP will allow us to construct robust and biologically meaningful classifiers for PTCL and will also allow us to idenfify therapeutically relevant oncogenic pathways and tumor/host interactions that would lead to improvement in the management of pafients with PTCL. Our aims are: 1) Identify key molecular signatures in PTCL and natural killer (NK) cell malignancies to construct a more robust and biologically meaningful classificafion. 2) Identify oncogenic pathways and tumor/host interacfions that contribute to the development of the neoplastic clone, tumor- induced immunosuppression and the outcome of patients with PTCL with particular emphasis on angioimmunoblasfic T-cell lymphoma (AITL). 3) To perform a phase l/ll trial in pafients with relapsed PTCL with agents that are directed at targets idenfified by GEP. Since PTCL is an uncommon disease, this study will draw on the fissue and clinical resources of several large completed and on-going projects for both discovery and validation. The participafion of two large medical centers (UNMC and M.D. Anderson) with strong emphasis on lymphoma management will provide the pafient population for the initial clinical trial. Additional efforts in the recruitment of subjects and involvement of other SPORES funded institufions are anficipated for the second trial based on the basic and clinical studies in the first two years of the project. We believe that this study will lead to novel targeted therapies that will significantly improve the outcome of patients with PTCL while reducing treatment related toxicity. RELEVANCE (See instructions): Most patients with PTCL have poor outcome with current chemotherapeufic regimens. Our proposal will lead to a better characterization of the disease including the oncogenic pathways that are often activated and the role of the microenvironmenL It will lead to novel therapeutic approaches that will improve survival of these pafients.

外周 T 细胞淋巴瘤 (PTCL) 是一种罕见的淋巴瘤，通常难以诊断和诊断 分类。大多数患者在标准多药化疗和新的、更多的化疗中生存率也很差 有效的治疗方法对于改善患者的治疗结果是必要的。我们使用基因的经验 研究 B 细胞淋巴瘤的表达谱分析 (GEP) 表明这种方法在治疗 B 细胞淋巴瘤方面非常有前景 改进分类、构建​​基于分子的预测器并检测生物学意义 可能成为治疗目标的途径。我们假设 GEP 将使我们能够构建稳健的 和具有生物学意义的 PTCL 分类器，也将使我们能够识别治疗相关的 致癌途径和肿瘤/宿主相互作用，这将导致改善管理 PTCL 患者。我们的目标是： 1) 识别 PTCL 和自然杀伤 (NK) 细胞的关键分子特征 恶性肿瘤以构建更稳健且具有生物学意义的分类。 2) 识别致癌物质 有助于肿瘤克隆、肿瘤- 诱导的免疫抑制和 PTCL 患者的结果，特别强调 血管免疫母细胞性 T 细胞淋巴瘤 (AITL)。 3) 在复发性PTCL患者中进行I/II期试验 与针对 GEP 确定的目标的代理。由于 PTCL 是一种罕见疾病，本研究 将利用几个已完成和正在进行的大型项目的组织和临床资源 发现和验证。两家大型医疗中心（UNMC 和 M.D. Anderson）的参与 对淋巴瘤管理的高度重视将为初次临床试验提供患者群体。 在受试者招募和其他 SPORES 资助机构的参与方面的额外努力是 基于该项目前两年的基础和临床研究，预计将进行第二次试验。 我们相信，这项研究将带来新的靶向疗法，从而显着改善治疗结果 PTCL 患者，同时减少治疗相关的毒性。 相关性（参见说明）： 大多数 PTCL 患者目前的化疗方案预后不佳。我们的建议将 导致更好地表征疾病，包括经常被激活和的致癌途径 微环境的作用将带来新的治疗方法，从而提高患者的生存率 这些病人。