Center for Multiple Myeloma Nanotherapy

 描述(由申请人提供)：华盛顿大学多发性骨髓瘤纳米治疗中心(WU CMMN)将解决骨恶性肿瘤的主要问题，重点是多发性骨髓瘤(MM)。多发性骨髓瘤是一种由终末分化的恶性浆B细胞引起的血液系统恶性肿瘤。骨髓瘤细胞同时激活骨髓中的骨吸收破骨细胞，抑制成骨细胞的形成，最终导致肿瘤生长和骨破坏的恶性循环。这种相互作用的一个可怕的结果是，80%的多发性骨髓瘤患者在确诊时会出现骨损害，包括病理性骨折。尽管多发性骨髓瘤患者的管理有了巨大的改善，但仅在2014年就发生了超过24,000例新病例和11,000例死亡。此外，化疗药物的副作用可能会增加全身毒性和住院费用的风险。受损的骨髓储备对如何在不产生恶化的细胞减少和进一步增加并发症风险的情况下最好地提供治疗施加了额外的限制。约10%的患者患有原发难治性疾病，对诱导治疗无效。因此，尽管较新的分子疗法可能会延长患者的生存时间，但几乎所有患者最终都会复发并死于MM。我们CMMN的长期目标是通过开发利用独特的药物传递机制和多维治疗范例来实现我们的目标的新型纳米疗法来提供治疗结果。以3个项目和两个核心为基础，我们的目标是(1)开发治疗多发性骨髓瘤的综合治疗方法，将非靶标毒性降至最低；(2)确定可用于临床翻译的纳米疗法；(3)提供一个平台，就癌症纳米医学的技术和方法对年轻研究人员和学生进行教育、培训和指导；(4)通过研讨会和研讨会为研究人员和患者创造富有成效的外联计划的环境；以及(5)与该地区的其他CCNE和研究人员合作，共享信息和资源，以期加速纳米医学向人类患者的临床翻译。除多发性骨髓瘤外，这项拟议研究的成功完成将全面推进血液疾病的治疗，并为解决骨髓转移治疗方面的挑战带来新的疗法。

 DESCRIPTION (provided by applicant): The Washington University Center for Multiple Myeloma Nanotherapy (WU CMMN) will address overarching questions in bone malignancies, with a focus on multiple myeloma (MM). MM is a hematopoietic malignancy caused by terminally differentiated malignant plasma B-cells. Myeloma cells simultaneously activate the bone resorbing osteoclast cells in the bone marrow and inhibit bone forming osteoblast cells, culminating in a vicious cycle of tumor growth and bone destruction. A grim result of this interplay is that 80% of MM patients present bone lesions including pathologic fracture at diagnosis. Despite tremendous improvements in MM patient management, more than 24,000 new cases and 11,000 deaths occurred in 2014 alone. Additionally, the side effects of chemotherapeutics can result in increased risk of systemic toxicity and hospitalization costs. An impaired bone marrow reserve imposes additional constraints on how best to deliver therapy without producing worsening cytopenias and further increasing the risk for complications. About 10% of patients have primary refractory disease and fail to respond to induction treatments. Thus, although newer molecular therapeutics may extend patient survival, nearly all patients will eventually relapse and die from MM. The long-term goal of our CMMN is to provide curative outcomes by developing novel nanotherapeutics that utilizes unique drug delivery mechanism and multidimensional treatment paradigms to accomplish our goal. Anchored by 3 projects and two cores, we aim to (1) develop integrated curative approach for the treatment of MM with minimal off target toxicity; (2) identify nanotherapeutics for clinical translation; (3) provide a platform to educate, train, and mentor young investigators and students on techniques and methods of cancer nanomedicine; (4) create environment for productive outreach programs that brings researchers and patients together through workshops and seminars; and (5) collaborate with other CCNEs and investigators in the region to share information and resources with a goal to accelerating clinical translation of nanomedicine to human patients. Beyond MM, successful completion of the proposed research will advance the treatment of hematological diseases in general and usher new therapies for tackling the challenges in treating bone marrow metastasis.