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12/9/2015 6:37:00 PM | Browse: 426 | Download: 560
Publication Name World Journal of Clinical Oncology
Manuscript ID 21154
Country/Territory Italy
2015-06-29 15:46
Peer-Review Started
2015-07-03 15:54
To Make the First Decision
2015-07-27 15:55
Return for Revision
2015-07-30 19:18
2015-09-07 00:00
Second Decision
2015-09-14 10:21
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief
2015-09-28 17:33
Articles in Press
2015-09-28 17:33
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript
2015-11-30 11:53
Publish the Manuscript Online
2015-12-09 18:37
ISSN 2218-4333 (online)
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/
Copyright © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Article Reprints For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
Permissions For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
Publisher Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Website http://www.wjgnet.com
Category Oncology
Manuscript Type Editorial
Article Title Neuroendocrine tumors resistant to mammalian target of rapamycin inhibitors: A difficult conversion from biology to the clinic
Manuscript Source Invited Manuscript
All Author List Nicola Fazio
Funding Agency and Grant Number
Corresponding author Nicola Fazio, MD, PhD, Unit of Gastroin­testinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Via Ripamonti, 43, 20141 Milan, Italy. nicola.fazio@ieo.it
Keywords Everolimus; BEZ235; Mammalian target of rapamycin; Phosphoinositide 3-kinase; Mammalian target of rapamycin C; Resistance; Mammalian target of rapamycin inhibitor
Core Tip Although everolimus significantly prolongs progression-free survival in patients with advanced pancreatic neuroendocrine tumors (NETs), some patients are refractory or progress early after an initial response. Mammalian target of rapamycin (mTOR) C2 and insulin growth factor (IGF) - IGF receptor signaling can mediate two supposed mechanisms of resistance to everolimus. BEZ235 is a multitargeted inhibitor binding to phosphoinositide 3-kinase, mTORC1 and mTORC2, therefore potentially turning off all the supposed mole-cular targets of resistance to everolimus. The two clinical trials designed in pancreatic NETs were stopped early due to unmet statistical endpoint and the global clinical development of BEZ235 was halted. Challenging tolerability probably conditioned the results. The BEZ experience is an example of the huge difference between preclinical and clinical setting and prompts us to pay more attention to the phase?Ⅰ?step of clinical development and the design of higher-phase trials.
Publish Date 2015-12-09 18:37
Citation Fazio N. Neuroendocrine tumors resistant to mammalian target of rapamycin inhibitors: A difficult conversion from biology to the clinic. World J Clin Oncol 2015; 6(6): 194-197
Url http://www.wjgnet.com/2218-4333/full/v6/i6/194.htm
DOI http://dx.doi.org/10.5306/wjco.v6.i6.194
Full Article (PDF) WJCO-6-194.pdf
Full Article (Word) WJCO-6-194.doc
Manuscript File 21154-Review.docx
Answering Reviewers 21154-Answering reviewers.pdf
Audio Core Tip 21154-Audio core tip.mp3
Conflict-of-Interest Disclosure Form 21154-Conflict-of-interest statement.pdf
Copyright License Agreement 21154-Copyright assignment.pdf
Non-Native Speakers of English Editing Certificate 21154-Language certificate.pdf
Peer-review Report 21154-Peer-review(s).pdf
Scientific Misconduct Check 21154-Scientific misconduct check.pdf
Scientific Editor Work List 21154-Scientific editor work list.pdf