Functional genomics lead to new therapies in follicular lymphoma.
Functional genomics lead to new therapies in follicular lymphoma.
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DOI：
10.1111/nyas.12120
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发表时间：
2013-07
影响因子：
5.2
通讯作者：
Wendel HG
中科院分区：
文献类型：
--
作者：
Oricchio E;Wendel HG
最近的技术进步使我们能够以前所未有的细节分析癌症的基因组变化。下一个挑战是对发现的大量基因畸变进行优先排序，并确定治疗机会。我们最近完成了一项研究，说明了使用无偏遗传筛选和小鼠癌症模型在复杂的基因组数据中寻找治疗靶点。我们对6q染色体的常见缺失进行了遗传解剖，并鉴定了ephrin受体A7 （EPHA7）在淋巴瘤中是一种肿瘤抑制因子。值得注意的是，EPHA7编码一种可溶性剪接变体，可作为外源性肿瘤抑制因子。因此，我们开发了一种基于抗体的策略，特异性地将EPHA7传递回失去该基因的肿瘤。最近的测序研究表明EPHA7与肺癌和其他肿瘤有关，这表明这种肿瘤抑制因子的抗体介导递送在癌症治疗中具有更广泛的治疗潜力。总之，我们的综合方法为癌症生物学提供了新的见解，并可能直接导致新的癌症治疗方法的发展。
Recent technological advances allow analysis of genomic changes in cancer in unprecedented detail. The next challenge is to prioritize the multitude of genetic aberrations found and identify therapeutic opportunities. We recently completed a study that illustrates the use of unbiased genetic screens and murine cancer models to find therapeutic targets among complex genomic data. We genetically dissected the common deletion of chromosome 6q and identified the ephrin receptor A7 (EPHA7) as a tumor suppressor in lymphoma. Notably, EPHA7 encodes a soluble splice variant that acts as an extrinsic tumor suppressor. Accordingly, we developed an antibody-based strategy to specifically deliver EPHA7 back to tumors that have lost this gene. Recent sequencing studies have implicated EPHA7 in lung cancer and other tumors, suggesting a broader therapeutic potential for antibody-mediated delivery of this tumor suppressor for cancer therapy. Together, our comprehensive approach provides new insights into cancer biology and may directly lead to the development of new cancer therapies.
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