High-throughput screens in cancer cell lines (CCLs) have been used for decades to help researchers identify compounds with the potential to improve the treatment of cancer and, more recently, to identify genomic susceptibilities in cancer via genome-wide shRNA and CRISPR/Cas9 screens. Additionally, rich genomic and transcriptomic data of these CCLs has allowed researchers to pair this screening data with biological features, enabling efforts to identify biomarkers of treatment response and gene dependencies. In this paper, we review the major CCL screening efforts and the large datasets these screens have made available. We also assess the CCL screens collectively and include a resource with harmonized CCL and compound identifiers to facilitate comparisons across screens. The CCLs in these screens were found to represent a wide range of cancer types, with a strong correlation between the representation of a cancer type and its associated mortality. Patient ages and gender distributions of CCLs were generally as expected, with some notable exceptions of female underrepresentation in certain disease types. Also, ethnicity information, while largely incomplete, suggests that African American and Hispanic patients may be severely underrepresented in these screens. Nearly all genes were targeted in the genetic perturbations screens, but the compounds used for the drug screens target less than half of known cancer drivers, likely reflecting known limitations in our drug design capabilities. Finally, we discuss recent developments in the field and the promise they hold for enabling future screens to overcome previous limitations and lead to new breakthroughs in cancer treatment.

中文翻译：

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不仅仅是寻找治愈方法：高通量癌细胞系筛选的前景和陷阱。


几十年来，癌细胞系 (CCL) 中的高通量筛选一直用于帮助研究人员识别有潜力改善癌症治疗的化合物，最近还通过全基因组 shRNA 和 CRISPR/Cas9 识别癌症的基因组敏感性屏幕。此外，这些 CCL 丰富的基因组和转录组数据使研究人员能够将这些筛选数据与生物学特征配对，从而能够识别治疗反应和基因依赖性的生物标志物。在本文中，我们回顾了主要的 CCL 筛选工作以及这些筛选提供的大型数据集。我们还对 CCL 筛选进行集体评估，并提供具有统一 CCL 和化合物标识符的资源，以方便跨筛选的比较。研究发现，这些筛查中的 CCL 代表了多种癌症类型，并且癌症类型的表现与其相关死亡率之间存在很强的相关性。 CCL 的患者年龄和性别分布总体上符合预期，但有一些明显的例外，即某些疾病类型中女性代表性不足。此外，种族信息虽然基本上不完整，但表明非裔美国人和西班牙裔患者在这些筛查中的代表性可能严重不足。几乎所有基因都是遗传扰动筛选的目标，但用于药物筛选的化合物只针对不到一半的已知癌症驱动因素，这可能反映了我们药物设计能力的已知局限性。最后，我们讨论了该领域的最新发展以及它们对使未来的屏幕能够克服以前的限制并带来癌症治疗新突破的承诺。