Targeting mTOR in Pancreatic Ductal Adenocarcinoma

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited, however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data has shown that inhibition of mechanistic target of rapamycin (mTOR) in spe...

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Main Authors: Sentia eIriana, Shahzad eAhmed, Jun eGong, Alagappan Anand Annamalai, Richard eTuli, Andrew Eugene Hendifar
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00099/full
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author Sentia eIriana
Shahzad eAhmed
Jun eGong
Jun eGong
Alagappan Anand Annamalai
Richard eTuli
Andrew Eugene Hendifar
author_facet Sentia eIriana
Shahzad eAhmed
Jun eGong
Jun eGong
Alagappan Anand Annamalai
Richard eTuli
Andrew Eugene Hendifar
author_sort Sentia eIriana
collection DOAJ
description Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited, however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data has shown that inhibition of mechanistic target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro as well as in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.
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spelling doaj.art-273b2851cee94b2b859f415e225b12f52022-12-21T20:11:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2016-04-01610.3389/fonc.2016.00099194914Targeting mTOR in Pancreatic Ductal AdenocarcinomaSentia eIriana0Shahzad eAhmed1Jun eGong2Jun eGong3Alagappan Anand Annamalai4Richard eTuli5Andrew Eugene Hendifar6Cedars-Sinai Medical CenterCedars-Sinai Medical CenterCity of Hope National Medical CenterCedars-Sinai Medical CenterCedars-Sinai Medical CenterCedars-Sinai Medical CenterCedars-Sinai Medical CenterTreatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited, however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data has shown that inhibition of mechanistic target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro as well as in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00099/fullClinical Trials as TopicpreclinicalKRASmTORPancreatic Ductal Adenocarcinoma
spellingShingle Sentia eIriana
Shahzad eAhmed
Jun eGong
Jun eGong
Alagappan Anand Annamalai
Richard eTuli
Andrew Eugene Hendifar
Targeting mTOR in Pancreatic Ductal Adenocarcinoma
Frontiers in Oncology
Clinical Trials as Topic
preclinical
KRAS
mTOR
Pancreatic Ductal Adenocarcinoma
title Targeting mTOR in Pancreatic Ductal Adenocarcinoma
title_full Targeting mTOR in Pancreatic Ductal Adenocarcinoma
title_fullStr Targeting mTOR in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Targeting mTOR in Pancreatic Ductal Adenocarcinoma
title_short Targeting mTOR in Pancreatic Ductal Adenocarcinoma
title_sort targeting mtor in pancreatic ductal adenocarcinoma
topic Clinical Trials as Topic
preclinical
KRAS
mTOR
Pancreatic Ductal Adenocarcinoma
url http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00099/full
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AT shahzadeahmed targetingmtorinpancreaticductaladenocarcinoma
AT junegong targetingmtorinpancreaticductaladenocarcinoma
AT junegong targetingmtorinpancreaticductaladenocarcinoma
AT alagappananandannamalai targetingmtorinpancreaticductaladenocarcinoma
AT richardetuli targetingmtorinpancreaticductaladenocarcinoma
AT andreweugenehendifar targetingmtorinpancreaticductaladenocarcinoma