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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (3): 256-263.doi: 10.3736/jcim20120303

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Advances in Smoothened-targeting therapies for pancreatic cancer: Implication for drug discovery from herbal medicines

Jin-bin Han, Yong-qiang Hua, Lian-yu Chen, Lu-ming Liu()   

  1. Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
  • Received:2011-08-28 Accepted:2011-11-21 Online:2012-03-20 Published:2018-04-15

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Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase Ⅰ clinical trials and some are in phase Ⅱ, meanwhile, phase Ⅰ or Ⅱ trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.

Key words: pancreatic neoplasms, neoplastic stem cells, smoothened, hedgehog proteins, signal transduction, plants, medicinal, review

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