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Ever since the German pathologist Rudolf Virchow made his famous thesis in 1855 that every cell originates from a cell (“omnis cellula e cellula”) it has become increasingly clear that cancer originates from a single cell in a tissue of origin. Since cancer also quite often is a caricature of the normal tissue homeostasis as highlighted by Pierce and Speers in 1988 much interest has been focused towards the specific cell of origin as a critical determinant of tumor phenotype. We are particularly interested in breast cancer which has been classified into at least five intrinsic subtypes reminiscent of different cellular phenotypes in the normal human breast. For a normal cell to accumulate aberrations it takes at least two fundamental events: cell division and permanent residency in the tissue. Therefore it has been speculated for decades that in general the most obvious candidate cell of origin of cancer is the somatic stem cell. Such cells divide and are considered long-term tenants. Indeed, intriguing new data from Bert Vogelstein’s laboratory suggest that there is a direct association between the life time number of stem cell divisions in a tissue and the risk of developing cancer. Experimental proof of a stem cell origin of cancer first came in 1997 from leukemia in John Dick’s laboratory. Later, in 2003 ,evidence was provided by Max Wicha and Michael Clarke demonstrating that also breast cancer rely on so-called tumor initiating cells or cancer stem cells for maintenance and progression. While it is tempting to assume that cancer stem cells originate from normal stem cells this remains an open question. As far as the breast is concerned any dividing cell with a long-term residency candidate for a cell-of-origin status. This explains why it is so pivotal to map the human breast stem cell hierarchy and gauge for transformation at different stages of differentiation. Determining the exact evolutionary trajectory of different subtypes will eventually lead to better preventive measures specifically targeting the relevant cells of origin and improvements of precision medicine.
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Breast cancer researchno. 1 (2024)
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Aylin Rizki, Valerie M. Weaver,Sun-Young Lee, Gabriela I. Rozenberg,Koei Chin, Connie A. Myers, Jamie L. Bascom, Joni D. Mott, Jeremy R. Semeiks, Leslie R. Grate, I. Saira Mian,Alexander D. Borowsky,Roy A. Jensen, Michael O. Idowu, Fanqing Chen,David J. Chen,Ole W. Petersen,Joe W. Gray, Mina J. Bissell
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ACTA PHYSIOLOGICA (2023)
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Aylin Rizki, Valerie M. Weaver,Sun-Young Lee, Gabriela I. Rozenberg,Koei Chin, Connie A. Myers, Jamie L. Bascom, Joni D. Mott, Jeremy R. Semeiks, Leslie R. Grate, I. Saira Mian,Alexander D. Borowsky,Roy A. Jensen,Michael O. Idowu, Fanqing Chen,David J. Chen,Ole W. Petersen,Joe W. Gray,Mina J. Bissell
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#Papers: 154
#Citation: 19756
H-Index: 48
G-Index: 140
Sociability: 6
Diversity: 0
Activity: 0
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