New therapeutics targeting colon cancer stem cells

Arun Thenappan, Ying Li, Kirti Shetty, Lynt Johnson, E. P. Reddy, Lopa Mishra

Research output: Contribution to journalArticle

Abstract

The recent identification of tumor-initiating colorectal cancer (CRC) stem cells in the pathogenesis of CRC has provided a potential target for novel therapeutics. Many details about CRC stem cells, however, remain poorly understood. Several potential markers of CRC stem cells have been proposed, including CD133, CD44, and, recently, Lgr5. Attention also has been drawn to control of stem cell self-renewal, proliferation, and differentiation by the Wnt and transforming growth factor (TGF)-β pathways. Disruption of Wnt signaling, via loss of APC (adenomatous polyposis coli), is among the earliest events in the multistage progression of CRC and likely occurs in basal crypt stem cells, generating a neoplastic cell population that then expands upward to occupy the rest of the crypt. TGF-β signaling is a key tumor suppressor pathway, and mutations in the type II receptor and Smad4 are observed in CRC specimens and are associated with more aggressive disease in tumors with disrupted Wnt signaling. Loss of the TGF-β adaptor protein β 2-spectrin is associated with loss of colonic cell polarity and architecture, and its expression parallels that of Smad4. This review suggests rational approaches to target CRC stem cells as a novel and effective way to treat advanced and difficult-to-treat CRC.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalCurrent Colorectal Cancer Reports
Volume5
Issue number4
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Neoplastic Stem Cells
Colonic Neoplasms
Colorectal Neoplasms
Transforming Growth Factors
Therapeutics
Genetic Suppression
Spectrin
Neoplasms
Cell Polarity
Adenomatous Polyposis Coli
Stem Cells

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Hepatology

Cite this

Thenappan, A., Li, Y., Shetty, K., Johnson, L., Reddy, E. P., & Mishra, L. (2009). New therapeutics targeting colon cancer stem cells. Current Colorectal Cancer Reports, 5(4), 209-216. https://doi.org/10.1007/s11888-009-0029-2

New therapeutics targeting colon cancer stem cells. / Thenappan, Arun; Li, Ying; Shetty, Kirti; Johnson, Lynt; Reddy, E. P.; Mishra, Lopa.

In: Current Colorectal Cancer Reports, Vol. 5, No. 4, 10.2009, p. 209-216.

Research output: Contribution to journalArticle

Thenappan, A, Li, Y, Shetty, K, Johnson, L, Reddy, EP & Mishra, L 2009, 'New therapeutics targeting colon cancer stem cells', Current Colorectal Cancer Reports, vol. 5, no. 4, pp. 209-216. https://doi.org/10.1007/s11888-009-0029-2
Thenappan A, Li Y, Shetty K, Johnson L, Reddy EP, Mishra L. New therapeutics targeting colon cancer stem cells. Current Colorectal Cancer Reports. 2009 Oct;5(4):209-216. https://doi.org/10.1007/s11888-009-0029-2
Thenappan, Arun ; Li, Ying ; Shetty, Kirti ; Johnson, Lynt ; Reddy, E. P. ; Mishra, Lopa. / New therapeutics targeting colon cancer stem cells. In: Current Colorectal Cancer Reports. 2009 ; Vol. 5, No. 4. pp. 209-216.
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