Molecular aspects of pancreatic cancer and future perspectives

Helmut Friess, Jörg Kleeff, Murray Korc, Markus W. Büchler

Research output: Contribution to journalReview article

71 Scopus citations

Abstract

Pancreatic cancer has one of the worst prognoses of all human malignancies and the molecular mechanisms underlying this aggressive disease have been extensively investigated in the past years. Tyrosine kinase growth factor receptors and their ligands act to influence tumor cell growth, differentiation, invasion, metastasis, and angiogenesis. In pancreatic cancer a variety of these growth factor receptors and ligands are expressed at increased levels and this overexpression influences the clinical course of the disease. For example, the concomitant presence of the EGF receptor and its ligands EGF, TGF-α, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. Furthermore, the growth inhibitory effects of the TGF-β superfamily of serine-threonine kinase receptors and their ligands are often blocked in pancreatic cancer cells. In addition to these alterations, mutations of the p53 tumor-suppressor gene, the K-ras proto-oncogene, and the Smad4 gene are frequently present in these tumors. Taken together, the abundance of growth-promoting factors, the disturbance of growth inhibitory pathways, and the presence of gene mutations combine to give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalDigestive Surgery
Volume16
Issue number4
DOIs
StatePublished - Aug 19 1999

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Keywords

  • Gene mutations
  • Gene therapy
  • Growth factors
  • Pancreatic cancer

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Friess, H., Kleeff, J., Korc, M., & Büchler, M. W. (1999). Molecular aspects of pancreatic cancer and future perspectives. Digestive Surgery, 16(4), 281-290. https://doi.org/10.1159/000018737