Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression

Heterogeneity within a tumour increases its ability to adapt to constantly changing constraints, but adversely affects a patient’s prognosis, therapy response and clinical outcome. Intratumoural heterogeneity results from a combination of extrinsic factors from the tumour microenvironment and intrin...

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Bibliographic Details
Published in:British journal of cancer Vol. 125; no. 2; pp. 164 - 175
Main Authors: Lüönd, Fabiana, Tiede, Stefanie, Christofori, Gerhard
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 20.07.2021
Nature Publishing Group
Subjects:
631/67/322
631/80/84/2176
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer Research
Cell Plasticity
Disease Progression
Drug Resistance
Drug Resistance, Neoplasm
Epidemiology
Epigenesis, Genetic
Epigenetics
Epithelial-Mesenchymal Transition
Female
Functional plasticity
Gene expression
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genetic Heterogeneity
Humans
Mesenchyme
Metastases
Microenvironments
Molecular Medicine
Oncology
Review
Review Article
Tumor microenvironment
Tumors
ISSN:0007-0920, 1532-1827, 1532-1827
Online Access:Get full text
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Summary:Heterogeneity within a tumour increases its ability to adapt to constantly changing constraints, but adversely affects a patient’s prognosis, therapy response and clinical outcome. Intratumoural heterogeneity results from a combination of extrinsic factors from the tumour microenvironment and intrinsic parameters from the cancer cells themselves, including their genetic, epigenetic and transcriptomic traits, their ability to proliferate, migrate and invade, and their stemness and plasticity attributes. Cell plasticity constitutes the ability of cancer cells to rapidly reprogramme their gene expression repertoire, to change their behaviour and identities, and to adapt to microenvironmental cues. These features also directly contribute to tumour heterogeneity and are critical for malignant tumour progression. In this article, we use breast cancer as an example of the origins of tumour heterogeneity (in particular, the mutational spectrum and clonal evolution of progressing tumours) and of tumour cell plasticity (in particular, that shown by tumour cells undergoing epithelial-to-mesenchymal transition), as well as considering interclonal cooperativity and cell plasticity as sources of cancer cell heterogeneity. We review current knowledge on the functional contribution of cell plasticity and tumour heterogeneity to malignant tumour progression, metastasis formation and therapy resistance.
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-021-01328-7