Stemness Signaling Pathways Are Dysregulated in Cancer Stem Cells

In normal stem cells, stemness signaling pathways are tightly controlled and genetically intact. In contrast, stemness signaling pathways in cancer stem cells (CSCs) are dysregulated, allowing these cells to self-renew and differentiate into cancers cells.1

Dysregulation of stemness signaling pathways contributes to CSCs’ resistance to chemotherapy and radiotherapy and to cancer recurrence and metastasis.

Cancer Stemness Signaling Pathways

Key stemness signaling pathways involved in the induction and maintenance of stemness in CSCs include2-4:

  • Wnt/β-catenin
  • Hedgehog
  • Notch
  • Nanog

Targeting these signaling pathways may disrupt aberrant signaling in CSCs, potentially reducing cancer recurrence and metastasis.5


  1. Ajani JA, Song S, Hochster HS, Steinberg IB. Cancer stem cells: the promise and the potential. Semin Oncol. 2015;42(suppl 1):S3-S17.
  2. Hoffmeyer K, Raggioli A, Rudloff S, et al. Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science. 2012;336(6088):1549-1554.
  3. Bourguignon LY, Earle C, Wong G, Spevak CC, Krueger K. Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene. 2012;31(2):149-160.
  4. Espinoza I, Pochampally R, Xing F, Watabe K, Miele L. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Therap. 2013;6:
  5. Boman BM, Huang E. Human colon cancer stem cells: a new paradigm in gastrointestinal
    oncology. J Clin Oncol. 2008;26(17):2828-2838.

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