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. 2013 May 6;13(1):40.
doi: 10.1186/1475-2867-13-40.

Cancer: a "stem-cell" disease?

Shi-Ming Tu  1
Affiliations

Cancer: a "stem-cell" disease?

Shi-Ming Tu. Cancer Cell Int. .

Abstract

Background: Nowadays, we believe that cancer is a genetic disease. We focus on the genetic targets and epigenetic changes in a tumor. Remarkably, many crucial signal pathways in a malignant cell involve "stem-ness" genes. The prevalence of stem-ness in cancer suggests that cancer has a stem-cell origin and is a stem-cell disease.

Presentation of the hypothesis: The observation that many innate stem-ness properties are easily interchangeable with malignant hallmarks needs to be further elucidated. There appears to be a malignant potential in every stem cell and a stem cell potential in every malignant cell. I hypothesize that cancer is a stem-cell disease rather than a genetic disease.

Testing the hypothesis: We will use homeobox genes to endow a certain progenitor cell with specific stem-ness properties and confer different stem-cell phenotypes to the particular cell type in a hierarchical manner. We will demonstrate that an earlier homeobox gene plus a genetic defect (such as Pten loss) tend to form a more virulent tumor, while a later homeobox gene plus the same genetic defect tend to express a more indolent phenotype. Importantly, we will show that in clinically relevant cancer subtypes, those with worse clinical outcomes may paradoxically harbor fewer genetic mutations than those with better outcomes do.

Implications of the hypothesis: The recognition that cancer is a stem-cell disease will instigate major paradigm shifts in our basic understanding of cancer. Many fundamental principles of oncology, such as multistep carcinogenesis, need to be reconciled. The realization that cancer is a stem-cell disease will also have profound clinical implications on personalized care. Many aspects of our current clinical trials need to be reevaluated.

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Figures

Figure 1
Figure 1
Cancer and stem cells. Cancer cells (top panel) and stem cells (bottom panel) are like mirror images of each other. There appears to be malignant potential in every stem cell and stem cell potential in every malignant cell. Reprinted with permission from Springer [2].
See this image and copyright information in PMC

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References

    1. Tu S-M, Lin S-H, Logothetis CJ. Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol. 2002;3:508–513. doi: 10.1016/S1470-2045(02)00820-3. - DOI - PubMed
    1. Tu S-M. In: Cancer treatment and research; vol. 154. Rosen ST, editor. New York: Springer; 2010. Origin of cancers. Clinical perspectives and implications of a stem-cell theory of cancer. - PubMed
    1. Virchow R. In: From demons and evil spirits to cancer genes. Fitzgerald PJ, editor. Washington DC: American Registry of Pathology; 2000. Die krankhaften geschwulste [in German]. 3 vols. Berlin: a hirschwald, 1863–1865.
    1. Pierce GB, Dixon FJ Jr. Testicular teratomas I. Demonstration of teratogenesis by metamorphosis of multipotential cells. Cancer. 1959;12:573–583. doi: 10.1002/1097-0142(195905/06)12:3<573::AID-CNCR2820120316>3.0.CO;2-M. - DOI - PubMed
    1. Stevens LC. Experimental production of testicular teratomas in mice. Proc Natl Acad Sci USA. 1964;52:654–661. doi: 10.1073/pnas.52.3.654. - DOI - PMC - PubMed