小柯机器人

美国布罗德研究所Kimberly Stegmaier、Francisca Vazquez等研究人员合作绘制出第一代儿科癌症依赖性图谱。该研究于2021年3月22日在线发表于国际一流学术期刊《自然—遗传学》。

研究人员表示，令人兴奋的治疗靶点正在通过高突变负担成人癌症CRISPR筛查发现。然而，一个关键问题是功能基因组方法是否会在儿科癌症中产生新的靶点，而这种突变以极少的突变而著称，这些突变通常编码被认为具有挑战性的药物靶标蛋白。

为了解决这个问题，研究人员创建了代表13种儿科实体和脑肿瘤类型的第一代儿科癌症依赖性图谱。研究人员对82个儿科癌细胞系进行了基因组规模的CRISPR–Cas9功能丧失筛选，并鉴定出细胞存活所需的基因。与小儿癌症具有较少体细胞突变的发现相反，研究人员发现与成年模型相比，小儿癌细胞系中遗传依赖性的复杂性相似。

儿科癌症依赖性图谱的发现为正在进行的精准医学临床试验提供了临床前支持。儿科癌症中观察到的靶点通常与成人癌症中的不同，这表明重新利用成人肿瘤药物将不足以解决儿童期癌症。

附：英文原文

Title: A first-generation pediatric cancer dependency map

Author: Neekesh V. Dharia, Guillaume Kugener, Lillian M. Guenther, Clare F. Malone, Adam D. Durbin, Andrew L. Hong, Thomas P. Howard, Pratiti Bandopadhayay, Caroline S. Wechsler, Iris Fung, Allison C. Warren, Joshua M. Dempster, John M. Krill-Burger, Brenton R. Paolella, Phoebe Moh, Nishant Jha, Andrew Tang, Philip Montgomery, Jesse S. Boehm, William C. Hahn, Charles W. M. Roberts, James M. McFarland, Aviad Tsherniak, Todd R. Golub, Francisca Vazquez, Kimberly Stegmaier

Issue&Volume: 2021-03-22

Abstract: Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered challenging drug targets. To address this, we created a first-generation pediatric cancer dependency map representing 13 pediatric solid and brain tumor types. Eighty-two pediatric cancer cell lines were subjected to genome-scale CRISPR–Cas9 loss-of-function screening to identify genes required for cell survival. In contrast to the finding that pediatric cancers harbor fewer somatic mutations, we found a similar complexity of genetic dependencies in pediatric cancer cell lines compared to that in adult models. Findings from the pediatric cancer dependency map provide preclinical support for ongoing precision medicine clinical trials. The vulnerabilities observed in pediatric cancers were often distinct from those in adult cancer, indicating that repurposing adult oncology drugs will be insufficient to address childhood cancers.

DOI: 10.1038/s41588-021-00819-w

Source: https://www.nature.com/articles/s41588-021-00819-w

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex