HARNESSING HOST RESPONSE TO PREVENT MYELOMA

总结 尽管有重大的治疗进展，但仍存在未满足的需要，以获得基本的 深入了解骨髓瘤（MM）的发病机制，并开发更新的方法， 预防临床恶性肿瘤。我们的研究计划将建立在我们以前的努力，在两个 领域-了解骨髓瘤的病因-发病机制和利用宿主反应 来预防癌症在最近的研究中，我们发现， 溶血脂质是近三分之一患者MM的病因学基础。我们还 开发了新的人源化小鼠模型，涵盖了整个恶性肿瘤谱， 包括前体国家。这些进展为下一步的研究奠定了基础， 了解脂质介导的炎症如何驱动骨髓瘤的发展， 了解这些途径可能会对机制产生影响。 在包括肥胖在内的不同状态下，潜在的脂质介导的炎症。MM及其 前驱态也是探索如何 利用适应性和先天免疫系统的生物学来预防癌症。

Summary In spite of major therapeutic advances there is an unmet need to gain fundamental insights into the pathogenesis of myeloma (MM) and develop newer approaches to prevent clinical malignancy. Our research program will build on our prior efforts in two areas- understanding the etio-pathogenesis of myeloma and harnessing host response to prevent cancer. In recent studies, we have discovered that chronic activation by lysolipids underlies the etiology of MM in nearly a third of patients. We have also developed new humanized mouse models that span the entire spectrum of malignancy, including precursor states. These advances set the stage for next studies to better understand how lipid-mediated inflammation may drive the development of myeloma and how to prevent it. Understanding these pathways may have implications for mechanisms underlying lipid-mediated inflammation in diverse states including obesity. MM and its precursor states are also an important model to probe basic questions about how to harness the biology of both adaptive and innate immune system to prevent cancer.