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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2016; 22(31): 6987-7005
Published online Aug 21, 2016. doi: 10.3748/wjg.v22.i31.6987
FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer
Chiara Caparello, Laura L Meijer, Ingrid Garajova, Alfredo Falcone, Tessa Y Le Large, Niccola Funel, Geert Kazemier, Godefridus J Peters, Enrico Vasile, Elisa Giovannetti
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy
Laura L Meijer, Ingrid Garajova, Tessa Y Le Large, Godefridus J Peters, Elisa Giovannetti, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Laura L Meijer, Tessa Y Le Large, Geert Kazemier, Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Ingrid Garajova, Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, Sant’Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy
Niccola Funel, Elisa Giovannetti, Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, 56124 Pisa, Italy
Niccola Funel, Elisa Giovannetti, CNR-Nano, Institute of Nanoscience and Nanotechnology, University of Pisa, 56124 Pisa, Italy
Author contributions: Caparello C, Meijer LL, Garajova I and Giovannetti E performed the literature research; Caparello C, Meijer LL and Giovannetti E wrote the paper; Le Large TY, Funel N and Falcone A reviewed the paper; Vasile E, Peters GJ and Kazemier G supervised the project.
Supported by AIRC/Start-Up (to Giovannetti E); Istituto Toscano Tumori ITT-2011 (to Caparello C, Funel N, Vasile E and Giovannetti E), Regione Toscana “Fas Salute” (to Funel N and Giovannetti E), Bennink Foundation (to Meijer LL, Le Large TY, Giovannetti E and Kazemier G), CCA Foundation (to Giovannetti E).
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Elisa Giovannetti, Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, via Paradisa, 2, 56124 Pisa, Italy. elisa.giovannetti@gmail.com
Telephone: +39-05-0996817 Fax: +39-05-0501095
Received: April 29, 2016
Peer-review started: May 2, 2016
First decision: May 30, 2016
Revised: June 9, 2016
Accepted: July 6, 2016
Article in press: July 6, 2016
Published online: August 21, 2016
Processing time: 108 Days and 6.5 Hours
Abstract

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase III trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARC levels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microRNAs as predictive biomarkers.

Keywords: FOLFIRINOX; Personalized therapy; New treatments; MicroRNA; Pancreatic cancer

Core tip: The present manuscript is a review of the state of the art treatments, focusing on biomarkers, target therapies and future perspectives in order to develop personalized treatments.