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

外周T细胞淋巴瘤（PTCL）是一种罕见的淋巴瘤，通常难以诊断， 分类。大多数患者在标准多药化疗和新的，更多的化疗后生存率也很差。 需要有效的治疗方法来改善患者的结果。我们使用基因的经验 表达proflling（GEP）研究B细胞淋巴瘤表明，这种方法是非常有前途的， 改进分类、构建分子标记物和检测生物学意义 可能成为治疗目标的途径。我们假设GEP将允许我们构建强大的 和生物学意义的分类PTCL，也将使我们能够证实治疗相关的 致癌途径和肿瘤/宿主相互作用，这将导致管理的改善 PTCL患者。我们的目标是：1）确定PTCL和自然杀伤（NK）细胞的关键分子特征 恶性肿瘤，以构建一个更强大和生物学意义的分类。2)鉴别致癌性 途径和肿瘤/宿主相互作用，有助于肿瘤克隆的发展，肿瘤- 诱导的免疫抑制和PTCL患者的结局，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 用的是针对GEP认证的目标的药剂。由于PTCL是一种罕见的疾病，本研究 将利用几个大型已完成和正在进行的项目的裂缝和临床资源， 发现和验证。两个大型医疗中心（UNMC和M.D.）的参与。安德森）与 对淋巴瘤管理的强调将为初始临床试验提供有效人群。 在招募受试者和其他SPORES资助机构的参与方面， 在前两年基础研究和临床研究的基础上，确定了第二次试验。 我们相信，这项研究将导致新的靶向治疗，将显着改善的结果， PTCL患者，同时降低治疗相关毒性。 相关性（参见说明）： 大多数PTCL患者在目前的化疗方案下结局较差。我们的建议将 导致更好地表征疾病，包括经常被激活的致癌途径， 它将导致新的治疗方法，将提高生存的微生物学的作用。 这些病人。

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.