mTOR is a promising therapeutical target in a subpopulation of pancreatic adenocarcinoma.
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.
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
Wesley K
WK
Utomo
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
Vilvapathy
V
Narayanan
Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Katharina
K
Biermann
Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
Casper H J
CH
van Eijck
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
Marco J
MJ
Bruno
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: m.peppelenbosch@erasmusmc.nl.
Maikel P
MP
Peppelenbosch
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
Henri
H
Braat
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
Flow cytometry; Pancreatic cancer; Personalized medicine; Rapamycin; mTOR