SPORE in Myeloma

简介（由申请人提供）：达纳法伯/哈佛癌症中心（DF/HCC）多发性骨髓瘤（MM）孢子更新申请包括6个研究项目和3个核心，以及职业发展和发展研究计划。在之前的融资期内，我们充分利用了哈佛附属机构（包括Dana- Farber癌症研究所、哈佛医学院、哈佛公共卫生学院以及梅奥诊所）在研究、临床专业知识和设施方面的互补优势。我们已经成功地将多种新型药物从实验室转化为临床治疗，并获得了FDA的批准，用于治疗MM。本次更新SPORE申请中的三个项目是从先前的开发项目发展而来的，两位职业发展奖获得者现在是新项目的首席研究员或联合研究员。其中一个新项目侧重于多民族人口的基因型和流行病学研究，反映了我们对少数民族研究的重视。我们已经在临床前细胞和分子研究以及联合临床方案方面建立了合作努力。该小组作为一个整体，具有必要的管理、基础科学和临床基础设施，长期致力于转化性MM研究。在这些建立良好的中心，每年评估超过750名新的MM患者，以及10,000名门诊就诊的浆细胞异常患者。评估的疾病范围从意义不明的单克隆伽玛病到浆细胞白血病。每个中心都有适当的科学和机构审查委员会，以及协议审计和质量控制中心，以进行尖端的转化研究。目前有超过50个有效的方案评估治疗方法，包括新药、免疫治疗、改良干细胞移植和支持治疗。这个庞大的合并患者基础确保了在这个项目中确定的新药治疗效果的快速积累和评估。该项目临床前和临床部分的成功将取决于这些中心之间的协同和沟通。为了实现这一目标，我们建立了一个互联网站点，允许所有主要研究人员访问共同研究工作中产生的临床前数据。同样，联合临床方案试验的数据也将存放在这个安全的网站上，以便在这些地点进行无缝和统一的临床研究。目前有系统的质量控制的骨髓和血液样本交换，用于相关的基础实验室研究。DF/HCC骨髓瘤孢子的总体主题是确定和评估新的靶向治疗方法。我们的大多数项目从一开始就源自临床研究，这突显了《孢子》的转化性质。具体项目有：(1)克服多发性骨髓瘤中蛋白酶体抑制剂耐药性；(2)靶向端粒扩张机制治疗骨髓瘤；(3)靶向Wnt通路治疗多发性骨髓瘤；(4) NF-?的靶向活化多发性骨髓瘤的B通路研究(5)浆细胞肿瘤演变的分子标记；(6)确定多发性骨髓瘤的高风险基因型：一项多民族病例对照研究。核心资源包括行政沟通和规划核心(1)，组织核心(2)，生物统计学和生物信息学核心(3)。

DESCRIPTION (provided by applicant): The Dana Farber/Harvard Cancer Center (DF/HCC) multiple myeloma (MM) SPORE renewal application consists of 6 Research Projects and 3 Cores, as well as the Career Development and Developmental Research Programs. During the previous funding period, we have capitalized on the complementary strengths of the research, clinical expertise, and facilities of the Harvard affiliated institutions including Dana- Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health, as well as the Mayo Clinic. We have successfully translated multiple novel agents from the bench to the bedside and FDA approval for treatment of MM. Three projects in this renewal SPORE application have evolved from prior Developmental Projects, and two Career Development awardees are now Principal Investigator or Co- Investigators of new projects. One of the new projects focuses on genotypic and epidemiologic studies in multi-ethnic population, reflecting our emphasis on minority studies. We have established a collaborative effort, both in preclinical cellular and molecular studies and in joint clinical protocols. The group as a whole has a long-term commitment to translational MM research, with the necessary administrative, basic science, and clinical infrastructure. At these well established centers, more than 750 new patients with MM are evaluated annually, as well as 10,000 outpatient visits for established patients with plasma cell dyscrasias. The spectrum of diseases evaluated spans from monoclonal gammopathy of unclear significance to plasma cell leukemia. Each center has appropriate scientific and institutional review boards, as well as protocol audit and quality control centers, to conduct cutting edge translational research. There are presently more than 50 active protocols evaluating therapies including novel drugs, immune treatments, improved stem cell transplantation, and supportive therapies in MM. This large combined patient base assures rapid accrual and evaluation of the therapeutic efficacy of novel agents identified in this program. Success of both the preclinical and clinical components of this Program will be dependent upon synergy and communication between these centers. To assure this end, we have set up an Internet site that allows access to all the Principal Investigators to the preclinical data generated in joint research efforts. Similarly, data from the joint clinical protocol trials will also be deposited in this secure web site to allow a seamless and uniform conduct of clinical studies at these sites. Currently there is systematic quality-controlled exchange of bone marrow and blood samples for correlative basic laboratory studies. The overall theme of the DF/HCC myeloma SPORE is to identify and evaluate novel targeted therapies. The translational nature of the SPORE is highlighted by the fact that most of our projects have emanated from clinical studies from the outset. Specific Projects are (1) Overcoming Proteasome-lnhibitor Resistance in Multiple Myeloma; (2) Targeting Telomere Expansion Mechanisms For Myeloma Therapy; (3) Targeting the Wnt Pathway for Treatment of Multiple Myeloma; (4) Targeting Activation of NF-?B Pathways in Multiple Myeloma; (5) Molecular Markers of Plasma Cell Neoplasm Evolution; and (6) Identifying High Risk Genotypes for Multiple Myeloma: A Collaborative Multi-Ethnic Case-Controlled Study. Core resources include Administrative Communication and Planning Core (1), Tissue Core (2), and Biostatistics and Bioinformatics Core (3). This Program therefore represents the integrated efforts of institutions with a unique and long track record of basic and clinical research expertise in MM, now joining together to more rapidly move rational novel targeted therapies from the laboratory to clinical protocols to improve patient outcome in MM.