Patkulkar Pooja Annasaheb, Subbalakshmi Ayalur Raghu, Jolly Mohit Kumar, Sinharay Sanhita
Centre for BioSystems Science and Engineering, Indian Institute of Science (IISc), Bangalore 560012, India.
ACS Omega. 2023 Feb 7;8(7):6126-6138. doi: 10.1021/acsomega.2c06659. eCollection 2023 Feb 21.
Intratumoral heterogeneity associates with more aggressive disease progression and worse patient outcomes. Understanding the reasons enabling the emergence of such heterogeneity remains incomplete, which restricts our ability to manage it from a therapeutic perspective. Technological advancements such as high-throughput molecular imaging, single-cell omics, and spatial transcriptomics allow recording of patterns of spatiotemporal heterogeneity in a longitudinal manner, thus offering insights into the multiscale dynamics of its evolution. Here, we review the latest technological trends and biological insights from molecular diagnostics as well as spatial transcriptomics, both of which have witnessed burgeoning growth in the recent past in terms of mapping heterogeneity within tumor cell types as well as the stromal constitution. We also discuss ongoing challenges, indicating possible ways to integrate insights across these methods to have a systems-level spatiotemporal map of heterogeneity in each tumor and a more systematic investigation of the implications of heterogeneity for patient outcomes.
肿瘤内异质性与更具侵袭性的疾病进展及更差的患者预后相关。对于导致这种异质性出现的原因，我们的理解仍不完整，这限制了我们从治疗角度对其进行管理的能力。诸如高通量分子成像、单细胞组学和空间转录组学等技术进步，使得能够纵向记录时空异质性模式，从而深入了解其进化的多尺度动态。在此，我们回顾分子诊断以及空间转录组学的最新技术趋势和生物学见解，这两者在绘制肿瘤细胞类型内的异质性以及基质构成方面，近年来都取得了蓬勃发展。我们还讨论了当前面临的挑战，指出整合这些方法的见解以获得每个肿瘤异质性的系统级时空图谱以及更系统地研究异质性对患者预后影响的可能途径。
