Unraveling the cartography of the cancer ecosystem

Abstract

Tumors are complex multifaceted ecosystems composed of malignant cells surrounded by a heterogeneous mixture of cell types. During oncogenesis, different populations of cancer cells interact with the microenvironment, contributing to evasion of the immune system and metastatic progression. One of the major goals for translational cancer research is to develop new technologies capable of unraveling this complexity across heterogeneous microenvironments. Bulk genomic and transcriptomic studies have uncovered major molecular insights and have helped in the design of patient-specific targeted therapeutics. Quantification of gene expression from bulk-sequencing approaches, however, only represents the average expression profiles of the constituent cells and is influenced by the particular transcriptional profiles, as well as the abundance of a multitude of different cell types and states within each sample. This becomes particularly relevant when considering the detection limits that might preclude the identification of low-level subclones. The development of technologies based on sequencing individual cells over the past decade has been astonishing. Notably, spatial molecular analysis of RNA and protein now place cellular biology at the center of cancer biology and may be used to dissect interactions across tumor microenvironments.