Molecular targets in diffuse large B cell lymphoma

描述（由申请人提供）：弥漫性大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤，在美国每年有25,000例发病率，每年有近10,000例死亡可归因于该疾病。虽然化疗是治疗的主要手段，但在过去的30年里，用于治疗DLBCL的化疗方案没有任何改进。在标准化疗中加入利妥昔单抗是治疗该疾病的重大进展。然而，只有约50%的患者在接受化疗和利妥昔单抗治疗后治愈。已有超过60项针对DLBCL患者的临床试验显示没有任何益处。许多DLBCL临床试验失败的一个重要原因可能是将疾病作为单一实体处理，尽管已知其分子异质性。DLBCL患者的基因表达谱表明，肿瘤至少包括两种不同的疾病，具有不同的起源细胞、不同的细胞遗传学差异和对蒽环类化疗方案的不同反应率。在这个提议中，我们展示了DLBCL的分子亚分类如何揭示了可以在临床中探索的新的肿瘤易感性。

DESCRIPTION (provided by applicant): Diffuse large B cell lymphoma (DLBCL) is the most common form of non Hodgkin lymphoma, with an annual incidence of 25,000 in the United States and nearly 10,000 deaths per year attributable to the disease. Although chemotherapy is the mainstay of therapy, there has been no improvement in the chemotherapy regimens used to treat DLBCL in the past 30 years. The addition of rituximab to standard chemotherapy has been a significant advance in the treatment of the disease. However, only about 50% of patients with this disease are cured after treatment with chemotherapy and rituximab. There have been over 60 clinical trials in patients with DLBCL that have demonstrated no benefit. An important reason for the failure of many clinical trials in DLBCL may be the approach to the disease as a single entity, even though it is known to be molecularly heterogeneous. Gene expression profiling of patients with DLBCL demonstrated that the tumors comprised at least two distinct diseases with different cells of origin, distinct cytogenetic differences and different response rates to anthracycline-based chemotherapy regimens. In this proposal, we demonstrate how the molecular subclassification of DLBCL reveals new tumor-susceptibilities that can be explored in the clinic.