Characterization of novel compounds with anti-lymphoma activity

描述（由申请人提供）：尽管美国癌症的发病率在过去十年中略有下降，但每年仍有50多万人死于癌症。存在大量不同类型的淋巴细胞恶性肿瘤，其代表B-和T-细胞发育的各个阶段，并且这些代表了这个国家所有癌症的大约9%。淋巴瘤占血细胞癌的约54%，主要形式是霍奇金淋巴瘤和非霍奇金淋巴瘤（NLH）。后者是最常见的淋巴瘤类型，影响高加索人的最高比率，其次是西班牙裔人。NLH患者的5年生存率约为67%，而非洲裔美国人的生存率较低，为56%。霍奇金淋巴瘤患者的白人生存率为83%，非洲裔美国人为77%。有许多因素不仅影响癌症发病率，而且影响死亡率，其中一些可能是观察到的健康差异的原因。不幸的是，找到治愈所有类型癌症的方法是极不可能的，因为有许多基因改变涉及许多不同类型的癌症。然而，有相当频繁的新药物被发现，通过靶向干扰其生长或诱导细胞死亡的特定途径来影响特定的癌症类型。最近几个月，我们开发并验证了一种筛选测定法，用于测试B细胞和T细胞淋巴瘤的小化合物库。这些筛选工作已经鉴定出对淋巴瘤具有高度细胞毒性的几种相关化合物。该项目的主要目标是表征已鉴定的新型抗淋巴瘤化合物。该项目的具体目标是（1）表征已鉴定的抗淋巴瘤化合物（2）确定先导化合物的作用模式，以及（3）检查最有前途的化合物在体内的作用。对特定类型的淋巴瘤具有细胞毒性的药物的鉴定和表征可以导致新的治疗剂。

DESCRIPTION (provided by applicant): Although the incidence for cancer in the US has declined slightly in the past decade, it still claims the lives of more than half a million individals a year. There are a great number of distinct types of lymphocyte malignancies that represent the various stages of B- and T-cell development and these represent approximately 9% of all cancers in this country. Lymphomas represent ~54% of blood cell cancers and the main forms are Hodgkin and non-Hodgkin lymphomas (NLH). The latter is the most common type of lymphoma and affects Caucasians at a highest rate followed closely by people of Hispanic descent. Patients with NLH have a 5 year survival rate of ~67% while African Americans have a lower survival rate of 56%. Patients with Hodgkin lymphoma have a survival rate of 83% for whites and 77% for African Americans. There are many factors that not only affect cancer incidence but also mortality, and some of these are the likely causes of the observed health disparities. Unfortunately, finding a cure for all types of cancer is highly unlikely as there are many genetic alterations that are involved and many distinct types of cancers. However, there are new drugs being discovered on a fairly frequent basis that affect specific cancer types by targeting specific pathways that interfere with their growth or induce cell death. In recent months, we have developed and validated a screening assay that was used to test a small library of compounds on B- and T-cell lymphomas. These screening efforts have resulted in the identification of several related compounds that are highly cytotoxic to lymphomas. The main goal of this project is to characterize the novel anti-lymphoma compounds that have been identified. The specific aims of the project are to (1) characterize the identified anti-lymphoma compounds (2) determine the mode of action of lead compounds, and (3) examine the effects of the most promising compounds in vivo. The identification and characterization of drugs that are cytotoxic to specific types of lymphomas can lead to novel therapeutic agents.