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，诊断和治疗往往具有挑战性。 分类。大多数患者接受标准的多药化疗和新的、更多的化疗后存活率也很低。 有效的治疗方法是改善患者预后所必需的。我们使用基因的经验 表达检测(GEP)研究B细胞淋巴瘤表明，这种方法在 改进分类，构建基于分子的预测指标，检测生物学意义 可能成为治疗靶点的途径。我们假设GEP将允许我们构建健壮的 以及对PTCL具有生物学意义的分类器，并将使我们能够识别与治疗相关的 致癌途径和肿瘤/宿主的相互作用将导致改善对 PTCL的情侣。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 以构建一个更可靠、更具生物学意义的分类方法。2)确定致癌因素 促进肿瘤克隆发展的途径和肿瘤/宿主相互作用，肿瘤- 诱导免疫抑制与PTCL患者的预后 血管免疫母细胞淋巴瘤(AITL)。3)对复发性PTCL患者进行L/11期试验 有针对GEP确认的目标的特工。由于PTCL是一种罕见的疾病，本研究 将利用几个已完成和正在进行的大型项目的fIssue和临床资源 发现和验证。两个大型医疗中心(UNMC和M.D.Anderson)的参与 对淋巴瘤治疗的高度重视将为最初的临床试验提供有症状的人群。 在招募受试者和其他孢子资助机构的参与方面的额外努力是 在项目头两年的基础和临床研究的基础上，进行了第二次试验。 我们相信，这项研究将导致新的靶向疗法，将显著改善结果 PTCL患者在减少治疗相关毒性的同时。 相关性(请参阅说明)： 大多数PTCL患者在目前的化疗方案中预后较差。我们的建议将 导致更好地描述疾病的特征，包括通常被激活和 微环境的作用这将导致新的治疗方法，将提高患者的存活率 这些情妇。

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.