Cancers display intratumoral and intertumoral heterogeneity, which poses challenges to small-molecule intervention. Studying drug responses on a whole-genome and transcriptome level using next-generation sequencing has revolutionized our understanding of how small molecules intervene in cells, which helps us to study and potentially predict treatment outcomes. Some small molecules act directly at the genomic level by targeting DNA or chromatin proteins. Here, we review recent advances in establishing whole-genome and transcriptome maps of small-molecule targets, comprising chromatin components or downstream events. We also describe recent advances in studying drug responses using single-cell RNA and DNA sequencing. Furthermore, we discuss how this fundamental research can be taken forward to devise innovative personalized treatment modalities.

中文翻译：

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癌症医学小分子靶标的全基因组定位。

癌症表现出肿瘤内和肿瘤间异质性，这对小分子干预构成了挑战。使用下一代测序技术在全基因组和转录组水平上研究药物反应，彻底改变了我们对小分子如何干预细胞的理解，这有助于我们研究并可能预测治疗结果。一些小分子通过靶向DNA或染色质蛋白而直接在基因组水平上起作用。在这里，我们审查建立小分子目标，包括染色质成分或下游事件的全基因组和转录组图谱的最新进展。我们还描述了使用单细胞RNA和DNA测序研究药物反应的最新进展。此外，我们讨论了如何开展这项基础研究来设计创新的个性化治疗方式。