Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies
Open Access
- 14 July 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 10 (1), 368
- https://doi.org/10.1186/1471-2407-10-368
Abstract
The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR) kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models.This publication has 19 references indexed in Scilit:
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic CancerJournal of Clinical Oncology, 2009
- Feedback Mechanisms Promote Cooperativity for Small Molecule Inhibitors of Epidermal and Insulin-Like Growth Factor ReceptorsCancer Research, 2008
- Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second‐line therapy for patients with advanced pancreatic cancerCancer, 2008
- Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid TumorsJournal of Clinical Oncology, 2008
- Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non–small-cell lung, pancreatic, colon, and breast tumorsMolecular Cancer Therapeutics, 2006
- Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanismOncogene, 2006
- The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferationBiochemical and Biophysical Research Communications, 2005
- A Randomized, Double-Blinded, Placebo-Controlled Phase II Trial of Recombinant Human Leukemia Inhibitory Factor (rhuLIF, Emfilermin, AM424) to Prevent Chemotherapy-Induced Peripheral NeuropathyClinical Cancer Research, 2005
- The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-κB and c-Myc in pancreatic cancer cellsOncogene, 2004