title: Interplay between autophagy and apoptosis in pancreatic tumors in response to gemcitabine.
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.
authors.affiliation: IDEHU-CONICET, Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 4° piso, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, dpapademetrio@ffyb.uba.ar.
authors.forename: Daniela Laura
authors.initials: DL
authors.lastname: Papademetrio
authors.forename: Victoria
authors.initials: V
authors.lastname: Cavaliere
authors.forename: Tania
authors.initials: T
authors.lastname: Simunovich
authors.forename: Susana
authors.initials: S
authors.lastname: Costantino
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Campos
authors.forename: Tomás
authors.initials: T
authors.lastname: Lombardo
authors.forename: Claudio Marcelo Fader
authors.initials: CM
authors.lastname: Kaiser
authors.forename: Elida
authors.initials: E
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine