Pancreatic cancer, a Mis-interpreter of the epigenetic language

Eriko Iguchi, Stephanie L. Safgren, David L. Marks, Rachel L. Olson, Martin E Fernandez-Zapico

Research output: Contribution to journalReview article

6 Scopus citations

Abstract

Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC†) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management. Over the past two decades, a model has been advanced of PDAC initiation and progression as a multi-step process driven by the acquisition of mutations leading to loss of tumor suppressors and activation of oncogenes. The recognition of the essential roles of these genetic alterations in the development of PDAC has revolutionized our knowledge of this disease. However, none of these findings have turned into effective treatment for this dismal malignancy. In recent years, studies in the areas of chromatin modifications, and non-coding RNAs have uncovered mechanisms for regulating gene expression which occur independently of genetic alterations. Chromatin-based mechanisms are interwoven with microRNA-driven regulation of protein translation to create an integrated epigenetic language, which is grossly dysregulated in PDAC. Thus in PDAC, key tumor suppressors that are well established to play a role in PDAC may be repressed, and oncogenes can be upregulated secondary to epigenetic alterations. Unlike mutations, epigenetic changes are potentially reversible. Given this feature of epigenetic mechanisms, it is conceivable that targeting epigenetic-based events promoting and maintaining PDAC could serve as foundation for the development of new therapeutic and diagnostic approaches for this disease.

Original languageEnglish (US)
Pages (from-to)575-590
Number of pages16
JournalYale Journal of Biology and Medicine
Volume89
Issue number4
StatePublished - Dec 1 2016

Keywords

  • Chromatin remodeling
  • Epigenomics
  • Gene expression
  • Non-coding RNAs
  • Pancreatic cancer

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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