The natural history of cancers can be understood through the lens of evolution given that the driving forces of cancer development are mutation and selection of fitter clones. Cancer growth and progression are spatial processes that involve the breakdown of normal tissue organization, invasion and metastasis. For these reasons, spatial patterns are an integral part of histological tumour grading and staging as they measure the progression from normal to malignant disease. Furthermore, tumour cells are part of an ecosystem of tumour cells and their surrounding tumour microenvironment. A range of new spatial genomic, transcriptomic and proteomic technologies offers new avenues for the study of cancer evolution with great molecular and spatial detail. These methods enable precise characterizations of the tumour microenvironment, cellular interactions therein and micro-anatomical structures. In conjunction with spatial genomics, it emerges that tumours and microenvironments co-evolve, which helps explain observable patterns of heterogeneity and offers new routes for therapeutic interventions.
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We would like to thank S. Dentro, I. Martincorena and T. Grünewald for critical feedback on the manuscript. L.R.Y. is funded by a Wellcome Trust Clinical Research Career Development Fellowship ref: 214584/Z/18/Z.
The authors declare no competing interests.
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- Adjuvant therapies
Cancer treatments given after primary therapy (particularly following surgical resection of a tumour) to reduce the risk of relapse.
- Carcinomas in situ
Neoplastic expansions of epithelial cells that are confined to the normal tissue structure in which they arose, without invasion of the adjacent stroma.
A clone is a population of cells that derive from a common ancestor. Cancers are found to be clones deriving from a single cell that expanded during the lifetime of a host. Clonal alterations are mutations that are present in all cells of a cancer because their occurrence preceded the expansion of the tumour.
- Immune-checkpoint blockade
A type of anticancer immunotherapy that blocks checkpoint proteins on T cells or their targets on cancer cells and promotes an immune response and killing of the tumour.
- Immune evasion
The process by which tumour cells develop several mechanisms that help them to continue to grow and expand by escaping immune control. Immune evasion is thought to be typically preceded by two other phases: elimination, when the immune system recognizes and eliminates tumour cells, and equilibrium, when the pressure from the immune system stalls tumour growth and expansion, and negative selection takes place.
The process of penetration and spread of cancer cells into the neighbouring normal tissue. In the case of carcinomas, invasion involves a breach of the basement membrane.
A process of cancer spreading from the primary disease site to lymph nodes or other organs, resulting in the formation of metastatic deposits known as metastases.
- Most recent common ancestor
In cancer evolution, the most recent founder cell from which all other tumour cells have directly descended.
Changes in the DNA sequence that are inherited across cell generations. Sources of mutation are erroneous replication, biochemical alterations of DNA and failed DNA repair. To date, all cells within the human body are found to accumulate mutations over their lifetime.
- Negative selection
The removal of deleterious variants from the population.
A tumour-specific antigen that is the result of a somatic coding mutation in the corresponding part of a gene. Antigens are protein fragments presented on the cell surface by the human leukocyte antigen (HLA) complex and recognized by different cells of the immune system.
- Positive selection
The spread of advantageous alleles within a population.
In evolution, natural selection denotes the process of survival and reproduction of the fittest organism within a given environment.
Further clones emerging within a tumour from one founder clone. Subclonal mutations are limited to a fraction of cancer cells and occur during tumour expansion.
- Tissue architecture
The micro-anatomical spatial organization of the tissue. Typical examples are layered epithelial tissues, glands and crypts. Tissue architecture can be combined with other means of tissue organization such as differentiation hierarchies.
- Tumour ecosystems
The collective set of heterogeneous cells in the vicinity of a tumour comprising cancer cells and the TME.
- Tumour microenvironment
(TME). A combination of non-tumour cells, such as stromal and immune cells, vessels, metabolites, signalling molecules, and other extracellular components among which tumour cells exist.
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Seferbekova, Z., Lomakin, A., Yates, L.R. et al. Spatial biology of cancer evolution. Nat Rev Genet (2022). https://doi.org/10.1038/s41576-022-00553-x