SPORE in Myeloma

描述（由申请人提供）：Dana Farber/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。在上一个资助期内，我们充分利用了哈佛附属机构的研究、临床专业知识和设施的互补优势，包括达纳-法伯癌症研究所、哈佛医学院、哈佛公共卫生学院以及马约诊所。我们已经成功地将多种新型药物从实验室转化为临床应用，并获得FDA批准用于治疗MM。此次更新SPORE申请中的三个项目是从之前的开发项目发展而来的，两名职业发展获奖者现在是新项目的主要研究者或共同研究者。其中一个新项目专注于多种族人群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关系。该小组作为一个整体长期致力于MM转化研究，并提供必要的行政、基础科学和临床基础设施。在这些完善的中心，每年评估750多名新的MM患者，以及10，000名患有浆细胞恶液质的确诊患者的门诊就诊。评估的疾病范围从意义不明的单克隆丙种球蛋白病到浆细胞白血病。每个中心都有适当的科学和机构审查委员会，以及方案审核和质量控制中心，以进行尖端的转化研究。目前有超过50个积极的协议评估治疗，包括新药，免疫治疗，改善干细胞移植，并在MM的支持疗法。这个大的合并患者基础，确保快速增长和评估的治疗效果的新药物在这个程序中确定。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作用和沟通。为了确保这一目标，我们建立了一个互联网网站，允许所有主要研究者访问联合研究工作中产生的临床前数据。同样，来自联合临床试验方案的数据也将存放在这个安全的网站上，以便在这些网站上无缝和统一地进行临床研究。目前，有系统的质量控制交换骨髓和血液样本，用于相关的基础实验室研究。DF/HCC骨髓瘤SPORE的总体主题是识别和评估新型靶向治疗。我们的大多数项目从一开始就源于临床研究，这一事实突出了SPORE的转化性质。具体项目有：（1）克服多发性骨髓瘤中的蛋白酶体抑制剂耐药性;（2）针对骨髓瘤治疗的端粒扩增机制;（3）针对多发性骨髓瘤治疗的Wnt通路;（4）针对NF-？多发性骨髓瘤中的B通路;（5）浆细胞肿瘤演变的分子标志物;（6）多发性骨髓瘤高风险基因型的鉴定：一项多种族病例对照研究。核心资源包括行政沟通和规划核心（1），组织核心（2）和生物统计学和生物信息学核心（3）。 因此，该计划代表了在MM基础和临床研究专业知识方面具有独特和长期记录的机构的综合努力，现在联合起来，更快地将合理的新型靶向治疗从实验室转移到临床方案，以改善MM患者的结局。

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.