mTOR is a promising therapeutical target in a subpopulation of pancreatic adenocarcinoma

Cancer Lett. 2014 May 1;346(2):309-17. doi: 10.1016/j.canlet.2014.01.014. Epub 2014 Jan 25.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease, unusually resistant against therapy. It is generally felt that stratification of patients for personalized medicine is the way forward. Here, we report that a subpopulation of PDACs shows strong activation of the mTOR signaling cassette. Moreover, we show that inhibition of mTOR in pancreatic cancer cell lines showing high levels of mTOR signaling is associated with cancer cell death. Finally, we show using fine needle biopsies the existence of a subpopulation of PDAC patients with high activation of the mTOR signaling cassette and provide evidence that inhibition of mTOR might be clinically useful for this group. Thus, our results define an unrecognized subpopulation of PDACs, characterized by high activation of mTOR and show that identification of this specific patient group in the early phase of diagnosis is feasible.

Keywords: Flow cytometry; Pancreatic cancer; Personalized medicine; Rapamycin; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Autophagy / drug effects
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / enzymology*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / pathology
  • Signal Transduction
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antibiotics, Antineoplastic
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus