Understanding intratumoral heterogeneity—the molecular variation among cells within a tumor—promises to address outstanding questions in cancer biology and improve the diagnosis and treatment of specific cancer subtypes. Single-cell analyses, especially RNA sequencing and other genomics modalities, have been transformative in revealing novel biomarkers and molecular regulators associated with tumor growth, metastasis and drug resistance. However, these approaches fail to provide a complete picture of tumor biology, as information on cellular location within the tumor microenvironment is lost. New technologies leveraging multiplexed fluorescence, DNA, RNA and isotope labeling enable the detection of tens to thousands of cancer subclones or molecular biomarkers within their native spatial context. The expeditious growth in these techniques, along with methods for multiomics data integration, promises to yield a more comprehensive understanding of cell-to-cell variation within and between individual tumors. Here we provide the current state and future perspectives on the spatial technologies expected to drive the next generation of research and diagnostic and therapeutic strategies for cancer.

了解肿瘤内异质性——肿瘤内细胞之间的分子变异——有望解决癌症生物学中的突出问题并改善特定癌症亚型的诊断和治疗。单细胞分析，尤其是 RNA 测序和其他基因组学模式，在揭示与肿瘤生长、转移和耐药性相关的新型生物标志物和分子调节剂方面具有变革性。然而，这些方法无法提供肿瘤生物学的完整图景，因为有关肿瘤微环境中细胞位置的信息丢失了。利用多重荧光、DNA、RNA 和同位素标记的新​​技术能够在其原生空间环境中检测数以万计的癌症亚克隆或分子生物标志物。这些技术的迅速发展，连同多组学数据集成的方法，有望更全面地了解单个肿瘤内部和之间的细胞间变异。在这里，我们提供了空间技术的当前状态和未来展望，这些技术有望推动下一代癌症研究以及诊断和治疗策略。