title: State of the art and future directions of pancreatic ductal adenocarcinoma therapy.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second cause of cancer-related death in 2030. PDAC is the poorest prognostic tumor of the digestive tract, with 80% of patients having advanced disease at diagnosis and 5-year survival rate not exceeding 7%. Until 2010, gemcitabine was the only validated therapy for advanced PDAC with a modest improvement in median overall survival as compared to best supportive care (5-6 vs 3 months). Multiple phase II-III studies have used various combinations of gemcitabine with other cytotoxics or targeted agents, most in vain, in attempt to improve this outcome. Over the past few years, the landscape of PDAC management has undergone major and rapid changes with the approval of the FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens in patients with metastatic disease. These two active combination chemotherapy options yield an improved median overall survival (11.1 vs 8.5 months, respectively) thus making longer survival a reasonably achievable goal. This breakthrough raises some new clinical questions about the management of PDAC. Moreover, better knowledge of the environmental and genetic events that underpin multistep carcinogenesis and of the microenvironment surrounding cancer cells in PDAC has open new perspectives and therapeutic opportunities. In this new dynamic context of deep transformation in basic research and clinical management aspects of the disease, we gathered updated preclinical and clinical data in a multifaceted review encompassing the lessons learned from the past, the yet unanswered questions, and the most promising research priorities to be addressed for the next 5 years.
authors: INSERM UMR1149, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France; Department of Digestive Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France; Department of Medical Oncology, Henri Mondor University Hospital, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Electronic address: cindy.neuzillet@orange.fr.
authors: Cindy
authors: C
authors: Neuzillet
authors: Department of Translational Research, AAREC Filia Research, 1 place Paul Verlaine, 92100 Boulogne-Billancourt, France.
authors: Annemilaï
authors: A
authors: Tijeras-Raballand
authors: Department of Clinical Pharmacy, Necker-Enfants Malades University Hospital, 149 Rue de Sèvres, 75015 Paris, France.
authors: Philippe
authors: P
authors: Bourget
authors: INSERM UMR1149, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France; Department of Pathology, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France.
authors: Jérôme
authors: J
authors: Cros
authors: INSERM UMR1149, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France; Department of Pathology, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France.
authors: Anne
authors: A
authors: Couvelard
authors: Department of Biliary and Pancreatic Surgery, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France.
authors: Alain
authors: A
authors: Sauvanet
authors: Department of Radiology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France.
authors: Marie-Pierre
authors: MP
authors: Vullierme
authors: Department of Medical Oncology, Henri Mondor University Hospital, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
authors: Christophe
authors: C
authors: Tournigand
authors: INSERM UMR1149, Bichat-Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 46 rue Henri Huchard, 75018 Paris, and 100 boulevard du Général Leclerc, 92110 Clichy, France; Department of Digestive Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France.
authors: Pascal
authors: P
authors: Hammel
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology
keywords: Chemotherapy; Imaging; Pancreatic cancer; Pathology; Radiotherapy; Targeted therapy