Mayo Clinic Multiple Myeloma SPORE

描述（由申请人提供）：多发性骨髓瘤（MM）是一种破坏性的血液恶性肿瘤，每年在美国影响超过20,000名新患者。它通常对DNA烷基化剂、糖皮质激素、蛋白酶体抑制剂和IMiD类免疫调节剂（沙利度胺、来那度胺和泊马度胺）的治疗反应良好。不幸的是，随着时间的推移，这种疾病对这些药物产生抗药性，患者复发并死亡。我们已经确定了4个关键的研究领域，它们有望转化为治疗患者的快速临床成果。1)采用新一代方法（如溶瘤病毒疗法）大力开发治疗MM的新策略；2)鉴于IMiDs的成功，研究具有抗mm活性的新型免疫调节剂，从SMAC模拟化合物开始；3)确定MM最常见突变的临床意义、MYC位点的结构重排、靶向MYC对MM患者的影响；4)探讨MM的克隆进化及其对耐药的影响。为了解决这些问题，我们从梅奥诊所的所有三个地点组建了一个专门的基础科学和临床研究人员团队，代表了世界上最大的MM项目。项目共同领导的强有力合作，以及三个共享资源核心——生物标本核心、生物统计学和生物信息学核心，以及行政核心，扩大了项目的规模。核心提供了工作和成本的经济性，并支持每个项目。最后，为了进一步加强MM研究，特别是4个项目的目标，该SPORE应用程序通过发展研究计划（例如，通过质谱法监测最小残留疾病的个体肽）和指导职业发展计划（例如，开发MM的新型免疫疗法）为年轻教师支持新的转化研究。梅奥诊所对MM研究的历史和机构承诺是无与伦比的，加上本孢子成员在MM研究方面在国内和国际上的领导作用，我们将能够迅速将我们的发现转化为MM患者的新治疗策略，不仅旨在控制，而且最终使治愈成为现实。

DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a devastating hematologic malignancy that affects over 20,000 new patients every year in the USA. It typically responds well to treatment with DNA alkylators, glucocorticoids, proteasome inhibitors, and the IMiD class of Immunomodulator (thalidomide, lenalidomide and pomalidomide). Unfortunately, over time the disease becomes resistant to these drugs and patients relapse and die. We have identified 4 key areas of research that promise to translate into rapid clinical gains for the treatment of patients. 1) Develop dramatically new strategies to treat MM using next-generation approaches such as oncolytic virotherapy; 2) Given the success of IMiDs, study novel classes of immunomodulators with anti-MM activity, starting with SMAC mimetic compounds; 3) Determine the clinical significance of the most frequent mutation in MM, structural rearrangements of the MYC locus, and the effects of targeting MYC in patients with MM; 4) Explore clonal evolution in MM, including its contribution to drug resistance. To tackle these issues we have assembled a dedicated team of basic science and clinical investigators from all three Mayo Clinic sites, representing the largest MM program in the world. The projects are augmented by the strong collaborations of the project co-leaders, and through the three shared resource cores: Biospecimens Core, Biostatistics and Bioinformatics Core, and Administrative Core. The cores provide economy of effort and cost and support each of the projects. Finally to further enhance MM research and specifically the Aims of the 4 projects, this SPORE application supports novel translational studies through a Developmental Research Program (e.g., individual peptide monitoring by mass spectrometry to follow minimal residual disease), and through a mentored Career Development Program (e.g., developing novel immune therapies for MM) for young faculty. The historical and institutional commitment to MM research at Mayo Clinic is unequalled, and together with the leading role nationally and internationally in MM research of members of this SPORE we will be able to quickly translate our discoveries into new treatment strategies for patients with MM aimed not just at control, but ultimately to make cure become a reality.