The Cellular Origin and Evolution of Breast Cancer

In this review, we will discuss how the cell of origin may modulate breast cancer intratumoral heterogeneity (ITH) as well as the role of ITH in the evolution of cancer. The clonal evolution and the cancer stem cell (CSC) models, as well as a model that integrates clonal evolution with a CSC hierarc...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in medicine 2017-03, Vol.7 (3), p.a027128
Main Authors: Zhang, Mei, Lee, Adrian V, Rosen, Jeffrey M
Format: Article
Language:English
Subjects:
Breast Neoplasms - genetics
Breast Neoplasms - therapy
Disease Progression
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Genetic Heterogeneity
Humans
Mutation
Neoplastic Stem Cells - metabolism
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Summary:In this review, we will discuss how the cell of origin may modulate breast cancer intratumoral heterogeneity (ITH) as well as the role of ITH in the evolution of cancer. The clonal evolution and the cancer stem cell (CSC) models, as well as a model that integrates clonal evolution with a CSC hierarchy, have all been proposed to explain the development of ITH. The extent of ITH correlates with clinical outcome and reflects the cellular complexity and dynamics within a tumor. A unique subtype of breast cancer, the claudin-low subtype that is highly resistant to chemotherapy and most closely resembles mammary epithelial stem cells, will be discussed. Furthermore, we will review how the interactions among various tumor cells, some with distinct mutations, may impact breast cancer treatment. Finally, novel technologies that may help advance our understanding of ITH and lead to improvements in the design of new treatments also will be discussed.
ISSN:2157-1422
2472-5412
DOI:10.1101/cshperspect.a027128