Deciphering the role of hedgehog signaling in pancreatic cancer

Dongsheng Gu, Kelly E. Schlotman, Jingwu Xie

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is a leading cause of cancer-related death in the US, with a dismal median survival of 6 months. Thus, there is an urgent unmet need to identify ways to diagnose and to treat this deadly cancer. Although a number of genetic changes have been identified in pancreatic cancer, their mechanisms of action in tumor development, progression and metastasis are not completely understood. Hedgehog signaling, which plays a major role in embryonic development and stem cell regulation, is known to be activated in pancreatic cancer; however, specific inhibitors targeting the smoothened molecule failed to improve the condition of pancreatic cancer patients in clinical trials. Furthermore, results regarding the role of Hh signaling in pancreatic cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive actions. In this review, we will summarize what we know about hedgehog signaling in pancreatic cancer, and try to explain the contradicting roles of hedgehog signaling as well as the reason(s) behind the failed clinical trials. In addition to the canonical hedgehog signaling, we will also discuss several non-canonical hedgehog signaling mechanisms.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalJournal of Biomedical Research
Volume30
Issue number5
DOIs
StatePublished - Jan 1 2016

Keywords

  • Cancer metastasis
  • Gli1
  • Non-canonical signaling
  • Pancreatic cancer
  • hedgehog

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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