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首要问题，重点是多发性骨髓瘤（MM）。MM是由终末分化的恶性浆B细胞引起的造血系统恶性肿瘤。骨髓瘤细胞同时激活骨髓中的骨吸收破骨细胞并抑制骨形成成骨细胞，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严峻结果是，80%的MM患者在诊断时出现骨病变，包括病理性骨折。尽管MM患者管理有了巨大的改善，但仅在2014年就发生了超过24，000例新发病例和11，000例死亡。此外，化疗药物的副作用可导致全身毒性和住院费用风险增加。骨髓储备受损对如何最好地提供治疗施加了额外的限制，而不会导致血细胞减少恶化并进一步增加并发症的风险。约10%的患者患有原发性难治性疾病，对诱导治疗无效。因此，虽然更新的分子治疗可能会延长患者的生存期，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新型纳米治疗剂来提供治愈性结局，该纳米治疗剂利用独特的药物递送机制和多维治疗范式来实现我们的目标。 由3个项目和两个核心锚定，我们的目标是（1）开发治疗MM的综合治疗方法，具有最小的脱靶毒性;（2）确定用于临床转化的纳米治疗药物;（3）提供一个平台，教育，培训和指导年轻的研究人员和学生癌症纳米医学的技术和方法;（4）通过讲习班和研讨会为富有成效的外展计划创造环境，将研究人员和患者聚集在一起;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，以加速纳米医学向人类的临床转化患者 除了MM，拟议研究的成功完成将推动血液病的治疗，并迎来新的治疗方法，以应对治疗骨髓转移的挑战。

 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.