Agents targeting the Hedgehog pathway for pancreatic cancer treatment

Savita Bisht, Peter Brossart, Anirban Maitra, Georg Feldmann

Research output: Contribution to journalArticlepeer-review

Abstract

Recent evidence has demonstrated that aberrant reactivation of the Hedgehog signaling pathway contributes to tumor initiation and progression in various human malignancies, including pancreatic cancer; therefore, the Hedgehog pathway has emerged as a promising novel therapeutic target. Initial translational studies conducted using cyclopamine, a small-molecule inhibitor of the Smoothened (SMO) component of the Hedgehog pathway, demonstrated that pharmacological blockade of aberrant Hedgehog signaling has the potential to inhibit tumor initiation, progression and metastatic spread. This concept has been corroborated using different compounds in various preclinical models of pancreatic cancer and other malignancies; several of these studies suggest possible therapeutic synergisms of Hedgehog inhibitors with established antineoplastic agents. This review provides a concise overview of translational studies assessing the use of Hedgehog inhibitors as novel therapeutic strategy for cancer, particularly pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1387-1398
Number of pages12
JournalCurrent Opinion in Investigational Drugs
Volume11
Issue number12
StatePublished - Dec 2010

Keywords

  • Cyclopamine
  • glioma-associated oncogene homolog
  • Hedgehog signaling
  • mouse model
  • pancreatic cancer
  • small-molecule inhibitor
  • Smoothened hedgehog
  • Sonic hedgehog
  • therapeutic target
  • translational research

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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