Cancer Research Targets Frontiers in Basic Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by O'Reilly, K. E.
Right arrow Articles by Rosen, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O'Reilly, K. E.
Right arrow Articles by Rosen, N.
[Cancer Research 66, 1500-1508, February 1, 2006]
© 2006 American Association for Cancer Research

Cell, Tumor, and Stem Cell Biology

mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt

Kathryn E. O'Reilly1, Fredi Rojo2, Qing-Bai She1, David Solit1, Gordon B. Mills3, Debra Smith3, Heidi Lane4, Francesco Hofmann4, Daniel J. Hicklin5, Dale L. Ludwig5, Jose Baselga2 and Neal Rosen1

1 Memorial Sloan-Kettering Cancer Center New York, New York; 2 Vall d'Hebron University Hospital, Barcelona, Spain; 3 The University of Texas M.D. Anderson Cancer Center, Houston, Texas; 4 Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland; and 5 ImClone Systems Incorporated, New York, New York

Requests for reprints: Neal Rosen, Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, Box 271, 1275 York Avenue, New York, NY 10021. Phone: 212-639-2369; Fax: 212-717-3627; E-mail: rosenn{at}mskcc.org.

Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin. Despite the activity in model systems, in patients, mTOR inhibitors exhibit more modest antitumor activity. We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001. IGF-I receptor inhibition prevents rapamycin-induced Akt activation and sensitizes tumor cells to inhibition of mTOR. In contrast, IGF-I reverses the antiproliferative effects of rapamycin in serum-free medium. The data suggest that feedback down-regulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation. Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity. (Cancer Res 2006; 66(3): 1500-8)




This article has been cited by other articles:


Home page
 Ann OncolHome page
S. Stacchiotti, A. Marrari, E. Tamborini, E. Palassini, E. Virdis, A. Messina, F. Crippa, C. Morosi, A. Gronchi, S. Pilotti, et al.
Response to imatinib plus sirolimus in advanced chordoma
Ann. Onc., July 1, 2009; (2009) mdp210v1.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. Tripathy
Are We Hitting the Right Combination for Hormonally Sensitive Breast Cancer?
J. Clin. Oncol., June 1, 2009; 27(16): 2580 - 2582.
[Full Text] [PDF]

Home page
 BrainHome page
M. W. Ronellenfitsch, D. P. Brucker, M. C. Burger, S. Wolking, F. Tritschler, J. Rieger, W. Wick, M. Weller, and J. P. Steinbach
Antagonism of the mammalian target of rapamycin selectively mediates metabolic effects of epidermal growth factor receptor inhibition and protects human malignant glioma cells from hypoxia-induced cell death
Brain, June 1, 2009; 132(6): 1509 - 1522.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. S.P. Yuen, E. Akkaya, Y. Wang, M. Takiguchi, S. Peak, M. Sullivan, A. S. Protheroe, and V. M. Macaulay
Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer
Mol. Cancer Ther., June 1, 2009; 8(6): 1448 - 1459.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. Meric-Bernstam and A. M. Gonzalez-Angulo
Targeting the mTOR Signaling Network for Cancer Therapy
J. Clin. Oncol., May 1, 2009; 27(13): 2278 - 2287.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Sabbatini, J. L. Rowand, A. Groy, S. Korenchuk, Q. Liu, C. Atkins, M. Dumble, J. Yang, K. Anderson, B. J. Wilson, et al.
Antitumor Activity of GSK1904529A, a Small-molecule Inhibitor of the Insulin-like Growth Factor-I Receptor Tyrosine Kinase
Clin. Cancer Res., May 1, 2009; 15(9): 3058 - 3067.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Breuleux, M. Klopfenstein, C. Stephan, C. A. Doughty, L. Barys, S.-M. Maira, D. Kwiatkowski, and H. A. Lane
Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition
Mol. Cancer Ther., April 1, 2009; 8(4): 742 - 753.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
S. H. KIM, K. ZUKOWSKI, and R. F. NOVAK
Rapamycin Effects on mTOR Signaling in Benign, Premalignant and Malignant Human Breast Epithelial Cells
Anticancer Res, April 1, 2009; 29(4): 1143 - 1150.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Toschi, E. Lee, L. Xu, A. Garcia, N. Gadir, and D. A. Foster
Regulation of mTORC1 and mTORC2 Complex Assembly by Phosphatidic Acid: Competition with Rapamycin
Mol. Cell. Biol., March 15, 2009; 29(6): 1411 - 1420.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Jimeno, W. A. Messersmith, F. R. Hirsch, W. A. Franklin, and S. G. Eckhardt
KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection
J. Clin. Oncol., March 1, 2009; 27(7): 1130 - 1136.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Daouti, H. Wang, W.-h. Li, B. Higgins, K. Kolinsky, K. Packman, A. Specian Jr., N. Kong, N. Huby, Y. Wen, et al.
Characterization of a Novel Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor with a Unique Mechanism of Action for Cancer Therapy
Cancer Res., March 1, 2009; 69(5): 1924 - 1932.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Copp, G. Manning, and T. Hunter
TORC-Specific Phosphorylation of Mammalian Target of Rapamycin (mTOR): Phospho-Ser2481 Is a Marker for Intact mTOR Signaling Complex 2
Cancer Res., March 1, 2009; 69(5): 1821 - 1827.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Marinov, A. Ziogas, O. E. Pardo, L. T. Tan, T. Dhillon, F. A. Mauri, H. A. Lane, N. R. Lemoine, U. Zangemeister-Wittke, M. J. Seckl, et al.
AKT/mTOR Pathway Activation and BCL-2 Family Proteins Modulate the Sensitivity of Human Small Cell Lung Cancer Cells to RAD001
Clin. Cancer Res., February 15, 2009; 15(4): 1277 - 1287.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
Y. Li, F. Guessous, C. DiPierro, Y. Zhang, T. Mudrick, L. Fuller, E. Johnson, L. Marcinkiewicz, M. Engelhardt, B. Kefas, et al.
Interactions between PTEN and the c-Met pathway in glioblastoma and implications for therapy
Mol. Cancer Ther., February 1, 2009; 8(2): 376 - 385.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Codeluppi, C. I. Svensson, M. P. Hefferan, F. Valencia, M. D. Silldorff, M. Oshiro, M. Marsala, and E. B. Pasquale
The Rheb-mTOR Pathway Is Upregulated in Reactive Astrocytes of the Injured Spinal Cord
J. Neurosci., January 28, 2009; 29(4): 1093 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
Q.-W. Fan, C. Cheng, Z. A. Knight, D. Haas-Kogan, D. Stokoe, C. D. James, F. McCormick, K. M. Shokat, and W. A. Weiss
EGFR Signals to mTOR Through PKC and Independently of Akt in Glioma
Sci. Signal., January 27, 2009; 2(55): ra4 - ra4.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J.-Y. Chung, S.-M. Hong, B. Y. Choi, H. Cho, E. Yu, and S. M. Hewitt
The Expression of Phospho-AKT, Phospho-mTOR, and PTEN in Extrahepatic Cholangiocarcinoma
Clin. Cancer Res., January 15, 2009; 15(2): 660 - 667.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. M. Wolpin, A. F. Hezel, T. Abrams, L. S. Blaszkowsky, J. A. Meyerhardt, J. A. Chan, P. C. Enzinger, B. Allen, J. W. Clark, D. P. Ryan, et al.
Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer
J. Clin. Oncol., January 10, 2009; 27(2): 193 - 198.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Prevention ResearchHome page
P. A. Dennis
Rapamycin for Chemoprevention of Upper Aerodigestive Tract Cancers
Cancer Prevention Research, January 1, 2009; 2(1): 7 - 9.
[Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. T. Ihle and G. Powis
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy
Mol. Cancer Ther., January 1, 2009; 8(1): 1 - 9.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
G. Desplanques, N. Giuliani, R. Delsignore, V. Rizzoli, R. Bataille, and S. Barille-Nion
Impact of XIAP protein levels on the survival of myeloma cells
Haematologica, January 1, 2009; 94(1): 87 - 93.
[Abstract] [Full Text] [PDF]

Home page
 Am Soc Clin Oncol Ed BookHome page
S. R.D. Johnston
Role of the mTOR Pathway in Endocrine-resistant Breast Cancer -- Opportunities for Novel Combination Strategies
ASCO Educational Book, January 1, 2009; 2009(1): 20 - 28.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Bianchini, M. Loiarro, P. Bielli, R. Busa, M. P. Paronetto, F. Loreni, R. Geremia, and C. Sette
Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells
Carcinogenesis, December 1, 2008; 29(12): 2279 - 2288.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. J.A. Eichhorn, M. Gili, M. Scaltriti, V. Serra, M. Guzman, W. Nijkamp, R. L. Beijersbergen, V. Valero, J. Seoane, R. Bernards, et al.
Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235
Cancer Res., November 15, 2008; 68(22): 9221 - 9230.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q. Xue, B. Hopkins, C. Perruzzi, D. Udayakumar, D. Sherris, and L. E. Benjamin
Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability
Cancer Res., November 15, 2008; 68(22): 9551 - 9557.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M. G. Crespo-Leiro and M. Hermida-Prieto
Sirolimus treatment of left ventricular hypertrophy: who, and when?
Eur. Heart J., November 2, 2008; 29(22): 2703 - 2704.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. M. Wilson, D. Barbone, T.-M. Yang, D. M. Jablons, R. Bueno, D. J. Sugarbaker, S. L. Nishimura, G. J. Gordon, and V. C. Broaddus
mTOR Mediates Survival Signals in Malignant Mesothelioma Grown as Tumor Fragment Spheroids
Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 576 - 583.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Buck, A. Eyzaguirre, M. Rosenfeld-Franklin, S. Thomson, M. Mulvihill, S. Barr, E. Brown, M. O'Connor, Y. Yao, J. Pachter, et al.
Feedback Mechanisms Promote Cooperativity for Small Molecule Inhibitors of Epidermal and Insulin-Like Growth Factor Receptors
Cancer Res., October 15, 2008; 68(20): 8322 - 8332.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Chaisuparat, J. Hu, B. C. Jham, Z. A. Knight, K. M. Shokat, and S. Montaner
Dual Inhibition of PI3K{alpha} and mTOR as an Alternative Treatment for Kaposi's Sarcoma
Cancer Res., October 15, 2008; 68(20): 8361 - 8368.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Serra, B. Markman, M. Scaltriti, P. J.A. Eichhorn, V. Valero, M. Guzman, M. L. Botero, E. Llonch, F. Atzori, S. Di Cosimo, et al.
NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
Cancer Res., October 1, 2008; 68(19): 8022 - 8030.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Ackler, Y. Xiao, M. J. Mitten, K. Foster, A. Oleksijew, M. Refici, S. Schlessinger, B. Wang, S. R. Chemburkar, J. Bauch, et al.
ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo
Mol. Cancer Ther., October 1, 2008; 7(10): 3265 - 3274.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Wang, P. Yue, Y. A. Kim, H. Fu, F. R. Khuri, and S.-Y. Sun
Enhancing Mammalian Target of Rapamycin (mTOR)-Targeted Cancer Therapy by Preventing mTOR/Raptor Inhibition-Initiated, mTOR/Rictor-Independent Akt Activation
Cancer Res., September 15, 2008; 68(18): 7409 - 7418.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. C. Yao, A. T. Phan, D. Z. Chang, R. A. Wolff, K. Hess, S. Gupta, C. Jacobs, J. E. Mares, A. N. Landgraf, A. Rashid, et al.
Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study
J. Clin. Oncol., September 10, 2008; 26(26): 4311 - 4318.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. L. Nakamura, E. Garcia, and R. O. Pieper
S6K1 Plays a Key Role in Glial Transformation
Cancer Res., August 15, 2008; 68(16): 6516 - 6523.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K.-F. Chen, P.-Y. Yeh, K.-H. Yeh, Y.-S. Lu, S.-Y. Huang, and A.-L. Cheng
Down-regulation of Phospho-Akt Is a Major Molecular Determinant of Bortezomib-Induced Apoptosis in Hepatocellular Carcinoma Cells
Cancer Res., August 15, 2008; 68(16): 6698 - 6707.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. R. Mills, Y. Hippo, F. Robert, S. M. H. Chen, A. Malina, C.-J. Lin, U. Trojahn, H.-G. Wendel, A. Charest, R. T. Bronson, et al.
mTORC1 promotes survival through translational control of Mcl-1
PNAS, August 5, 2008; 105(31): 10853 - 10858.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Stemke-Hale, A. M. Gonzalez-Angulo, A. Lluch, R. M. Neve, W.-L. Kuo, M. Davies, M. Carey, Z. Hu, Y. Guan, A. Sahin, et al.
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer
Cancer Res., August 1, 2008; 68(15): 6084 - 6091.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Opel, M.-A. Westhoff, A. Bender, V. Braun, K.-M. Debatin, and S. Fulda
Phosphatidylinositol 3-Kinase Inhibition Broadly Sensitizes Glioblastoma Cells to Death Receptor- and Drug-Induced Apoptosis
Cancer Res., August 1, 2008; 68(15): 6271 - 6280.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Shimamura, D. Li, H. Ji, H. J. Haringsma, E. Liniker, C. L. Borgman, A. M. Lowell, Y. Minami, K. McNamara, S. A. Perera, et al.
Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Cancer Res., July 15, 2008; 68(14): 5827 - 5838.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Q. Lacy, M. Alsina, R. Fonseca, M. L. Paccagnella, C. L. Melvin, D. Yin, A. Sharma, M. Enriquez Sarano, M. Pollak, S. Jagannath, et al.
Phase I, Pharmacokinetic and Pharmacodynamic Study of the Anti-Insulinlike Growth Factor Type 1 Receptor Monoclonal Antibody CP-751,871 in Patients With Multiple Myeloma
J. Clin. Oncol., July 1, 2008; 26(19): 3196 - 3203.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Soni, A. Akcakanat, G. Singh, D. Luyimbazi, Y. Zheng, D. Kim, A. Gonzalez-Angulo, and F. Meric-Bernstam
eIF4E knockdown decreases breast cancer cell growth without activating Akt signaling
Mol. Cancer Ther., July 1, 2008; 7(7): 1782 - 1788.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
A. Sekulic, P. Haluska Jr, A. J. Miller, J. G. De Lamo, S. Ejadi, J. S. Pulido, D. R. Salomao, E. C. Thorland, R. G. Vile, D. L. Swanson, et al.
Malignant Melanoma in the 21st Century: The Emerging Molecular Landscape
Mayo Clin. Proc., July 1, 2008; 83(7): 825 - 846.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S.-M. Maira, F. Stauffer, J. Brueggen, P. Furet, C. Schnell, C. Fritsch, S. Brachmann, P. Chene, A. De Pover, K. Schoemaker, et al.
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
Mol. Cancer Ther., July 1, 2008; 7(7): 1851 - 1863.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Tarn, L. Rink, E. Merkel, D. Flieder, H. Pathak, D. Koumbi, J. R. Testa, B. Eisenberg, M. von Mehren, and A. K. Godwin
Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors
PNAS, June 17, 2008; 105(24): 8387 - 8392.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
H. C. Dan, M. J. Cooper, P. C. Cogswell, J. A. Duncan, J. P.-Y. Ting, and A. S. Baldwin
Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK
Genes & Dev., June 1, 2008; 22(11): 1490 - 1500.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. A. Garcia and D. Danielpour
Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies
Mol. Cancer Ther., June 1, 2008; 7(6): 1347 - 1354.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. K. Mann, M. Colombo, and W. H. Miller Jr.
Arsenic trioxide decreases AKT protein in a caspase-dependent manner
Mol. Cancer Ther., June 1, 2008; 7(6): 1680 - 1687.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. M.W. Verheul, B. Salumbides, K. Van Erp, H. Hammers, D. Z. Qian, T. Sanni, P. Atadja, and R. Pili
Combination Strategy Targeting the Hypoxia Inducible Factor-1{alpha} with Mammalian Target of Rapamycin and Histone Deacetylase Inhibitors
Clin. Cancer Res., June 1, 2008; 14(11): 3589 - 3597.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Meikle, K. Pollizzi, A. Egnor, I. Kramvis, H. Lane, M. Sahin, and D. J. Kwiatkowski
Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function
J. Neurosci., May 21, 2008; 28(21): 5422 - 5432.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
G. Johansson, Y. Y. Mahller, M. H. Collins, M.-O. Kim, T. Nobukuni, J. Perentesis, T. P. Cripe, H. A. Lane, S. C. Kozma, G. Thomas, et al.
Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors
Mol. Cancer Ther., May 1, 2008; 7(5): 1237 - 1245.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. H. Lu, W. Wu, B. Dave, B. M. Slomovitz, T. W. Burke, M. F. Munsell, R. R. Broaddus, and C. L. Walker
Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma
Clin. Cancer Res., May 1, 2008; 14(9): 2543 - 2550.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Rhodes, D. A. Heerding, D. R. Duckett, D. J. Eberwein, V. B. Knick, T. J. Lansing, R. T. McConnell, T. M. Gilmer, S.-Y. Zhang, K. Robell, et al.
Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity
Cancer Res., April 1, 2008; 68(7): 2366 - 2374.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. O'Donnell, S. Faivre, H. A. Burris III, D. Rea, V. Papadimitrakopoulou, N. Shand, H. A. Lane, K. Hazell, U. Zoellner, J. M. Kovarik, et al.
Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Patients With Advanced Solid Tumors
J. Clin. Oncol., April 1, 2008; 26(10): 1588 - 1595.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. Tabernero, F. Rojo, E. Calvo, H. Burris, I. Judson, K. Hazell, E. Martinelli, S. R. y Cajal, S. Jones, L. Vidal, et al.
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 Tumors
J. Clin. Oncol., April 1, 2008; 26(10): 1603 - 1610.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. Zhong, X. Liu, K. Schafer-Hales, A. I. Marcus, F. R. Khuri, S.-Y. Sun, and W. Zhou
2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition
Mol. Cancer Ther., April 1, 2008; 7(4): 809 - 817.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. C. McDonald, A. Oloumi, J. Mills, I. Dobreva, M. Maidan, V. Gray, E. D. Wederell, M. B. Bally, L. J. Foster, and S. Dedhar
Rictor and Integrin-Linked Kinase Interact and Regulate Akt Phosphorylation and Cancer Cell Survival
Cancer Res., March 15, 2008; 68(6): 1618 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Kong, S. Banerjee, W. Huang, Y. Li, Z. Wang, H.-R. C. Kim, and F. H. Sarkar
Mammalian Target of Rapamycin Repression by 3,3'-Diindolylmethane Inhibits Invasion and Angiogenesis in Platelet-Derived Growth Factor-D-Overexpressing PC3 Cells
Cancer Res., March 15, 2008; 68(6): 1927 - 1934.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
A. Moreno, A. Akcakanat, M. F Munsell, A. Soni, J. C Yao, and F. Meric-Bernstam
Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors
Endocr. Relat. Cancer, March 1, 2008; 15(1): 257 - 266.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Hegedus, D. Banerjee, T.-H. Yeh, S. Rothermich, A. Perry, J. B. Rubin, J. R. Garbow, and D. H. Gutmann
Preclinical Cancer Therapy in a Mouse Model of Neurofibromatosis-1 Optic Glioma
Cancer Res., March 1, 2008; 68(5): 1520 - 1528.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. H. Oh, Q. Jin, E. S. Kim, F. R. Khuri, and H.-Y. Lee
Insulin-like Growth Factor-I Receptor Signaling Pathway Induces Resistance to the Apoptotic Activities of SCH66336 (Lonafarnib) through Akt/Mammalian Target of Rapamycin-Mediated Increases in Survivin Expression
Clin. Cancer Res., March 1, 2008; 14(5): 1581 - 1589.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. A. Brandes, E. Franceschi, A. Tosoni, M. E. Hegi, and R. Stupp
Epidermal Growth Factor Receptor Inhibitors in Neuro-oncology: Hopes and Disappointments
Clin. Cancer Res., February 15, 2008; 14(4): 957 - 960.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M.-E. Legrier, C.-P. H. Yang, H.-G. Yan, L. Lopez-Barcons, S. M. Keller, R. Perez-Soler, S. B. Horwitz, and H. M. McDaid
Targeting Protein Translation in Human Non Small Cell Lung Cancer via Combined MEK and Mammalian Target of Rapamycin Suppression
Cancer Res., December 1, 2007; 67(23): 11300 - 11308.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
X. Wang, P. Yue, C.-B. Chan, K. Ye, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, H. Fu, F. R. Khuri, and S.-Y. Sun
Inhibition of Mammalian Target of Rapamycin Induces Phosphatidylinositol 3-Kinase-Dependent and Mnk-Mediated Eukaryotic Translation Initiation Factor 4E Phosphorylation
Mol. Cell. Biol., November 1, 2007; 27(21): 7405 - 7413.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Fouladi, F. Laningham, J. Wu, M. A. O'Shaughnessy, K. Molina, A. Broniscer, S. L. Spunt, I. Luckett, C. F. Stewart, P. J. Houghton, et al.
Phase I Study of Everolimus in Pediatric Patients With Refractory Solid Tumors
J. Clin. Oncol., October 20, 2007; 25(30): 4806 - 4812.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. A. Finlay, A. J. Malhowski, Y. Liu, B. L. Fanburg, D. J. Kwiatkowski, and D. Toksoz
Selective Inhibition of Growth of Tuberous Sclerosis Complex 2 Null Cells by Atorvastatin Is Associated with Impaired Rheb and Rho GTPase Function and Reduced mTOR/S6 Kinase Activity
Cancer Res., October 15, 2007; 67(20): 9878 - 9886.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C.-H. Lu, S. L. Wyszomierski, L.-M. Tseng, M.-H. Sun, K.-H. Lan, C. L. Neal, G. B. Mills, G. N. Hortobagyi, F. J. Esteva, and D. Yu
Preclinical Testing of Clinically Applicable Strategies for Overcoming Trastuzumab Resistance Caused by PTEN Deficiency
Clin. Cancer Res., October 1, 2007; 13(19): 5883 - 5888.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Q. Lun, H. Zhou, T. Alain, B. Sun, L. Wang, J. W. Barrett, M. M. Stanford, G. McFadden, J. Bell, D. L. Senger, et al.
Targeting Human Medulloblastoma: Oncolytic Virotherapy with Myxoma Virus Is Enhanced by Rapamycin
Cancer Res., September 15, 2007; 67(18): 8818 - 8827.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. L. Kwak, J. W. Clark, and B. Chabner
Targeted Agents: The Rules of Combination
Clin. Cancer Res., September 15, 2007; 13(18): 5232 - 5237.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. K. Rowinsky, H. Youssoufian, J. R. Tonra, P. Solomon, D. Burtrum, and D. L. Ludwig
IMC-A12, a Human IgG1 Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor
Clin. Cancer Res., September 15, 2007; 13(18): 5549s - 5555s.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q.-W. Fan, C. K. Cheng, T. P. Nicolaides, C. S. Hackett, Z. A. Knight, K. M. Shokat, and W. A. Weiss
A Dual Phosphoinositide-3-Kinase {alpha}/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN-Mutant Glioma
Cancer Res., September 1, 2007; 67(17): 7960 - 7965.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. J. Riely, M. G. Kris, B. Zhao, T. Akhurst, D. T. Milton, E. Moore, L. Tyson, W. Pao, N. A. Rizvi, L. H. Schwartz, et al.
Prospective Assessment of Discontinuation and Reinitiation of Erlotinib or Gefitinib in Patients with Acquired Resistance to Erlotinib or Gefitinib Followed by the Addition of Everolimus
Clin. Cancer Res., September 1, 2007; 13(17): 5150 - 5155.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. B. Hjelmeland, K. P. Lattimore, B. E. Fee, Q. Shi, S. Wickman, S. T. Keir, M. D. Hjelmeland, D. Batt, D. D. Bigner, H. S. Friedman, et al.
The combination of novel low molecular weight inhibitors of RAF (LBT613) and target of rapamycin (RAD001) decreases glioma proliferation and invasion
Mol. Cancer Ther., September 1, 2007; 6(9): 2449 - 2457.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. M. Ballou, E. S. Selinger, J. Y. Choi, D. G. Drueckhammer, and R. Z. Lin
Inhibition of Mammalian Target of Rapamycin Signaling by 2-(Morpholin-1-yl)pyrimido[2,1-{alpha}]isoquinolin-4-one
J. Biol. Chem., August 17, 2007; 282(33): 24463 - 24470.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. A. Crowell, V. E. Steele, and J. R. Fay
Targeting the AKT protein kinase for cancer chemoprevention
Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. D. Mosley, J. T. Poirier, D. D. Seachrist, M. D. Landis, and R. A. Keri
Rapamycin inhibits multiple stages of c-Neu/ErbB2 induced tumor progression in a transgenic mouse model of HER2-positive breast cancer
Mol. Cancer Ther., August 1, 2007; 6(8): 2188 - 2197.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
I Duran, R Salazar, O Casanovas, V Arrazubi, E Vilar, L. Siu, J Yao, and J Tabernero
New drug development in digestive neuroendocrine tumors
Ann. Onc., August 1, 2007; 18(8): 1307 - 1313.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
T. C. Vary, G. Deiter, and C. J. Lynch
Rapamycin Limits Formation of Active Eukaryotic Initiation Factor 4F Complex Following Meal Feeding in Rat Hearts
J. Nutr., August 1, 2007; 137(8): 1857 - 1862.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. E. Johnson, D. Jackman, and P. A. Janne
Rationale for a Phase I Trial of Erlotinib and the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) for Patients with Relapsed Non Small Cell Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4628s - 4631s.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. A. Engelman
The Role of Phosphoinositide 3-Kinase Pathway Inhibitors in the Treatment of Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4637s - 4640s.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
X. Wan and L. J. Helman
The Biology Behind mTOR Inhibition in Sarcoma
Oncologist, August 1, 2007; 12(8): 1007 - 1018.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. M. Johnson, B. Saigal, H. Tran, and N. J. Donato
Abrogation of Signal Transducer and Activator of Transcription 3 Reactivation after Src Kinase Inhibition Results in Synergistic Antitumor Effects
Clin. Cancer Res., July 15, 2007; 13(14): 4233 - 4244.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
L. Kopelovich, J. R. Fay, C. C. Sigman, and J. A. Crowell
The Mammalian Target of Rapamycin Pathway as a Potential Target for Cancer Chemoprevention
Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1330 - 1340.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. L. Phung, G. Eyiah-Mensah, R. K. O'Donnell, R. Bieniek, S. Shechter, K. Walsh, C. Kuperwasser, and L. E. Benjamin
Endothelial Akt Signaling Is Rate-Limiting for Rapamycin Inhibition of Mouse Mammary Tumor Progression
Cancer Res., June 1, 2007; 67(11): 5070 - 5075.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. T. Abraham and J. J. Gibbons
The Mammalian Target of Rapamycin Signaling Pathway: Twists and Turns in the Road to Cancer Therapy
Clin. Cancer Res., June 1, 2007; 13(11): 3109 - 3114.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R. T. Kurmasheva, F. C. Harwood, and P. J. Houghton
Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors
Mol. Cancer Ther., May 1, 2007; 6(5): 1620 - 1628.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z. Zeng, D. D. Sarbassov, I. J. Samudio, K. W. L. Yee, M. F. Munsell, C. Ellen Jackson, F. J. Giles, D. M. Sabatini, M. Andreeff, and M. Konopleva
Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Blood, April 15, 2007; 109(8): 3509 - 3512.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. F. Petricoin III, V. Espina, R. P. Araujo, B. Midura, C. Yeung, X. Wan, G. S. Eichler, D. J. Johann Jr., S. Qualman, M. Tsokos, et al.
Phosphoprotein Pathway Mapping: Akt/Mammalian Target of Rapamycin Activation Is Negatively Associated with Childhood Rhabdomyosarcoma Survival
Cancer Res., April 1, 2007; 67(7): 3431 - 3440.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Mabuchi, D. A. Altomare, D. C. Connolly, A. Klein-Szanto, S. Litwin, M. K. Hoelzle, H. H. Hensley, T. C. Hamilton, and J. R. Testa
RAD001 (Everolimus) Delays Tumor Onset and Progression in a Transgenic Mouse Model of Ovarian Cancer
Cancer Res., March 15, 2007; 67(6): 2408 - 2413.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. L. Arteaga
Will Single-Time Tumor Profiling and a "Guilt by Association" Approach Allow Us to Outsmart HER2-Positive Breast Cancer?
Clin. Cancer Res., February 15, 2007; 13(4): 1071 - 1073.
[Full Text] [PDF]

Home page
 J. Virol.Home page
M. M. Stanford, J. W. Barrett, S. H. Nazarian, S. Werden, and G. McFadden
Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells
J. Virol., February 1, 2007; 81(3): 1251 - 1260.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
I. K. Mellinghoff, T. F. Cloughesy, and P. S. Mischel
PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors
Clin. Cancer Res., January 15, 2007; 13(2): 378 - 381.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Rojo, L. Najera, J. Lirola, J. Jimenez, M. Guzman, M. D. Sabadell, J. Baselga, and S. R. y Cajal
4E-Binding Protein 1, A Cell Signaling Hallmark in Breast Cancer that Correlates with Pathologic Grade and Prognosis
Clin. Cancer Res., January 1, 2007; 13(1): 81 - 89.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
S. Melmed
Acromegaly
N. Engl. J. Med., December 14, 2006; 355(24): 2558 - 2573.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
M. I. Torres-Arzayus, J. Yuan, J. L. DellaGatta, H. Lane, A. L. Kung, and M. Brown
Targeting the AIB1 Oncogene through Mammalian Target of Rapamycin Inhibition in the Mammary Gland
Cancer Res., December 1, 2006; 66(23): 11381 - 11388.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Mateo-Lozano, P. C. Gokhale, V. A. Soldatenkov, A. Dritschilo, O. M. Tirado, and V. Notario
Combined Transcriptional and Translational Targeting of EWS/FLI-1 in Ewing's Sarcoma.
Clin. Cancer Res., November 15, 2006; 12(22): 6781 - 6790.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
E. Buck, A. Eyzaguirre, E. Brown, F. Petti, S. McCormack, J. D. Haley, K. K. Iwata, N. W. Gibson, and G. Griffin
Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non-small-cell lung, pancreatic, colon, and breast tumors.
Mol. Cancer Ther., November 1, 2006; 5(11): 2676 - 2684.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
O. J. Shah and T. Hunter
Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis.
Mol. Cell. Biol., September 1, 2006; 26(17): 6425 - 6434.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.