Sommer Elijah R, Napoli Giulia C, Chau Cindy H, Price Douglas K, Figg William D
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
iScience. 2023 Feb 10;26(3):106174. doi: 10.1016/j.isci.2023.106174. eCollection 2023 Mar 17.
Identification of actionable drug targets remains a rate-limiting step of, and one of the most prominent barriers to successful drug development for metastatic cancers. CRISPR-Cas9, a tool for making targeted genomic edits, has given rise to various novel applications that have greatly accelerated discovery in developmental biology. Recent work has coupled a CRISPR-Cas9-based lineage tracing platform with single-cell transcriptomics in the unexplored context of cancer metastasis. In this perspective, we briefly reflect on the development of these distinct technological advances and the process by which they have become integrated. We also highlight the importance of single-cell lineage tracing in oncology drug development and suggest the profound capacity of a high-resolution, computational approach to reshape cancer drug discovery by enabling identification of novel metastasis-specific drug targets and mechanisms of resistance.
确定可作用的药物靶点仍然是转移性癌症成功药物开发的限速步骤之一，也是最突出的障碍之一。CRISPR-Cas9是一种用于进行靶向基因组编辑的工具，它催生了各种新应用，极大地加速了发育生物学领域的发现。最近的研究工作将基于CRISPR-Cas9的谱系追踪平台与单细胞转录组学相结合，应用于尚未探索的癌症转移领域。从这个角度出发，我们简要回顾了这些不同技术进展的发展历程以及它们整合的过程。我们还强调了单细胞谱系追踪在肿瘤学药物开发中的重要性，并指出高分辨率计算方法通过识别新的转移特异性药物靶点和耐药机制，具有重塑癌症药物发现的巨大潜力。
