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Published in: Targeted Oncology 2/2014

01-06-2014 | Original Research

Interplay between autophagy and apoptosis in pancreatic tumors in response to gemcitabine

Authors: Daniela Laura Papademetrio, Victoria Cavaliere, Tania Simunovich, Susana Costantino, María Dolores Campos, Tomás Lombardo, Claudio Marcelo Fader Kaiser, Élida Álvarez

Published in: Targeted Oncology | Issue 2/2014

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Abstract

Pancreatic cancer is an aggressive disease. Its incidence has increased over the last two decades. It is currently the fourth cause of death among cancers in the western world. Unfortunately, systemic chemotherapy still relies on just a few drugs which until now have produced unsatisfactory results. Gemcitabine (2′-2′-difluorodeoxycytidine) is currently the standard chemotherapy treatment at all stages of pancreatic adenocarcinoma. Survival benefit and clinical impact however remain moderate due to a high degree of intrinsic and acquired resistance. Autophagy plays an important role in cell death decision but can also protect cells from various apoptotic stimuli. We investigated the function of autophagy in pancreatic carcinoma cells, which are frequently insensitive to standard chemotherapeutic agents. Here, we demonstrate that autophagy is one of the mechanisms responsible for the refractory response of pancreatic tumors to gemcitabine. We present evidence in vitro and in vivo that proves autophagy plays a protective role in pancreatic ductal carcinoma cells, preventing them from entering the apoptotic pathway after stimulus with gemcitabine, thus contributing to treatment resistance. A better understanding of the role in the process may help in the discovery of new strategies to overcome tumor drug resistance in this aggressive disease.
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Metadata
Title
Interplay between autophagy and apoptosis in pancreatic tumors in response to gemcitabine
Authors
Daniela Laura Papademetrio
Victoria Cavaliere
Tania Simunovich
Susana Costantino
María Dolores Campos
Tomás Lombardo
Claudio Marcelo Fader Kaiser
Élida Álvarez
Publication date
01-06-2014
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 2/2014
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-013-0278-5

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