HARNESSING HOST RESPONSE TO PREVENT MYELOMA

摘要 尽管在治疗方面取得了重大进展，但仍有一种尚未得到满足的基本需求 对骨髓瘤(MM)发病机制的洞察和开发新的治疗方法 预防临床恶变。我们的研究计划将在两年内建立在我们先前努力的基础上 领域-了解骨髓瘤的病因和发病机制并利用宿主反应 来预防癌症。在最近的研究中，我们发现慢性激活通过 在近三分之一的患者中，溶脂是多发性骨髓瘤病因的基础。我们还有 开发了一种新的人性化小鼠模型，这种模型跨越了整个恶性肿瘤的范围， 包括前身国家。这些进展为下一步更好的研究奠定了基础 了解脂质介导的炎症可能如何推动骨髓瘤的发展和 如何防止它的发生。了解这些途径可能会对机制产生影响 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ITS 前兆状态也是探索以下基本问题的重要模型： 利用适应性免疫系统和先天免疫系统的生物学特性来预防癌症。

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.