Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

Wander, Seth A.; Hennessy, Bryan T.; Slingerland, Joyce M.

doi:10.1172/jci44145

Cited by 429PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesMetabolism, Diabetes, and Cancer

Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

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Wander, Seth A., Hennessy, Bryan T., Slingerland, Joyce M.·2011·Journal of Clinical Investigation

DOI 10.1172/jci44145PMC PMC3069769

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Abstract

Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

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mTOR inhibition with rapamycin and newly developed agents may prevent the appearance of radiation-induced mucositis and its consequent negative impact on anticancer treatment outcome and cost.
“our findings indicate that by preserving the tissue repopulating capacity of the epithelial stem cells, mTOR inhibition with rapamycin and newly developed agents (Wander et al., 2011) may prevent the appearance of radiation-induced mucositis and its consequent negative impact on anticancer treatment outcome and cost”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Wander et al., 2011
Treatments targeting key components of tumor hypoxia signaling pathways, including mTOR, are current approaches to cancer therapy.
“Treatments targeting key components of tumor hypoxia signaling pathways, including mTOR, are one of the current approaches to cancer therapy.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [182]

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Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15593 · Cited by 4,285 · see citing works
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · see citing works
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092 · see citing works
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · see citing works
Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma
Hudes, G. R., Carducci, M. A., Tomczak, P., Dutcher, J. P., Figlin, R. A., Kapoor, A., Starosławska, E., Sosman, J. A., McDermott, D. F., Bodrogi, I., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066838 · Cited by 3,645 · see citing works
A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance
Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165 · see citing works
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.
Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,135 · see citing works
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., Grünwald, V., Thompson, J. A., Figlin, R. A., Hollaender, N., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61039-9 · Cited by 3,019 · see citing works
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,722 · see citing works
Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,659 · see citing works
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561 · see citing works
ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions
Roux, P. P., & Blenis, J. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.2.320-344.2004 · Cited by 2,494 · see citing works
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445 · see citing works
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337 · see citing works
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130 · see citing works
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950 · see citing works
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803 · see citing works
Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.
Vézina, C., KUDELSKI, A., & Sehgal, S. N. (1975) · The Journal of Antibiotics · doi:10.7164/antibiotics.28.721 · Cited by 1,691 · see citing works
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650 · see citing works
Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00568-3 · Cited by 1,555 · see citing works
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
Medema, R. H., Kops, G. J. P. L., Bos, J. L., & Burgering, B. M. T. (2000) · Nature · doi:10.1038/35008115 · Cited by 1,439 · see citing works
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384 · see citing works
Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
Carracedo, A., Ma, L., Teruya-Feldstein, J., Rojo, F., Salmena, L., Alimonti, A., Egia, A., Sasaki, A. T., Thomas, G., Kozma, S. C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34739 · Cited by 1,381 · see citing works
The nuts and bolts of AGC protein kinases
Pearce, L. R., Komander, D., & Alessi, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2822 · Cited by 1,294 · see citing works
Phosphorylation and Functional Inactivation of TSC2 by Erk
Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268 · see citing works
Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis
Bissler, J. J., McCormack, F. X., Young, L. R., Elwing, J., Chuck, G., Leonard, J. M., Schmithorst, V. J., Laor, T., Brody, A. S., Bean, J. A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa063564 · Cited by 1,250 · see citing works
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237 · see citing works
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235 · see citing works
Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · see citing works
DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival
Peterson, T. R., Laplante, M., Thoreen, C. C., Sancak, Y., Kang, S. A., Kuehl, W. M., Gray, N. S., & Sabatini, D. M. (2009) · Cell · doi:10.1016/j.cell.2009.03.046 · Cited by 1,202 · see citing works
Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells
Zhou, B. P., Liao, Y., Xia, W., Spohn, B., Lee, M., & Hung, M. (2001) · Nature Cell Biology · doi:10.1038/35060032 · Cited by 1,135 · see citing works
The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins
Harrington, L. S., Findlay, G. M., Gray, A., Толкачева, Т. А., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403069 · Cited by 1,123 · see citing works
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D., & Shokat, K. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000038 · Cited by 1,080 · see citing works
The LKB1 tumor suppressor negatively regulates mTOR signaling
Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,067 · see citing works
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
Neshat, M., Mellinghoff, I., Tran, C., Stiles, B. L., Thomas, G., Petersen, R., Frost, P., Gibbons, J., Wu, H., & Sawyers, C. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.171076798 · Cited by 1,033 · see citing works
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
Krueger, D. A., Caré, M. M., Holland, K. D., Agricola, K. D., Tudor, C., Mangeshkar, P., Wilson, K. A., Byars, A. W., Sahmoud, T., & Franz, D. N. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001671 · Cited by 1,003 · see citing works
The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy
Chu, I. M., Hengst, L., & Slingerland, J. M. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2347 · Cited by 986 · see citing works
Self-citation
Akt regulates growth by directly phosphorylating Tsc2
Potter, C. J., Pedraza, L. G., & Xu, T. (2002) · Nature Cell Biology · doi:10.1038/ncb840 · Cited by 959 · see citing works
PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest
Liang, J., Zubovitz, J., Petrocelli, T., Kotchetkov, R., Connor, M. K., Han, K. C.-Z., Lee, J.-H., Ciarallo, S., Catzavelos, C., Beniston, R., et al. (2002) · Nature Medicine · doi:10.1038/nm761 · Cited by 947 · see citing works
Self-citation
Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell Carcinoma
Atkins, M. B., Hidalgo, M. M., Stadler, W. M., Logan, T. F., Dutcher, J. P., Hudes, G. R., Park, Y., Liou, S.-H., Marshall, B., Boni, J. P., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.185 · Cited by 942 · see citing works
mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907 · see citing works
Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression
Liang, J., & Slingerland, J. M. (2003) · Cell Cycle · doi:10.4161/cc.2.4.433 · Cited by 885 · see citing works
Self-citation
The PTEN–PI3K pathway: of feedbacks and cross-talks
Carracedo, A., & Pandolfi, P. P. (2008) · Oncogene · doi:10.1038/onc.2008.247 · Cited by 883 · see citing works
The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis
Liang, J., Shao, S. H., Xu, Z.-X., Hennessy, B. T., Ding, Z., Larrea, M. D., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1537 · Cited by 868 · see citing works
Self-citation
Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation
Choo, A. Y., Yoon, S.-O., Kim, S. G., Roux, P. P., & Blenis, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809136105 · Cited by 813 · see citing works
AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity
Chresta, C. M., Davies, B. R., Hickson, I., Harding, T. C., Cosulich, S. C., Critchlow, S. E., Vincent, J. P., Ellston, R. P. A., Jones, D., Sini, P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1751 · Cited by 796 · see citing works
NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
Serra, V., Markman, B., Scaltriti, M., Eichhorn, P. J. A., Valero, V., Guzman, M., Botero, M. L., Llonch, E., Atzori, F., Di Cosimo, S., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1385 · Cited by 787 · see citing works
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase
Roux, P. P., Ballif, B. A., Anjum, R., Gygi, S. P., & Blenis, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405659101 · Cited by 750 · see citing works
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
Frödin, M., & Gammeltoft, S. (1999) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(99)00061-1 · Cited by 716 · see citing works
Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling
DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W. (2008) · Genes & Development · doi:10.1101/gad.1617608 · Cited by 710 · see citing works
Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study
Galanis, E., Buckner, J. C., Maurer, M. J., Kreisberg, J. I., Ballman, K. V., Boni, J. P., Peralba, J. M., Jenkins, R. B., Dakhil, S. R., Morton, R. F., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.23.622 · Cited by 690 · see citing works
Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study
Yao, J. C., Phan, A. T., Chang, D. Z., Wolff, R. A., Hess, K. R., Gupta, S. K., Jacob, C., Mares, J. E., Landgraf, A., Rashid, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.7858 · Cited by 649 · see citing works
Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Heß, G., Herbrecht, R., Romaguera, J. E., Verhoef, G. E. G., Crump, M., Gisselbrecht, C., Laurell, A., Offner, F. C., Strahs, A. L., Berkenblit, A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.7977 · Cited by 641 · see citing works
Targeting the mTOR Signaling Network for Cancer Therapy
Meric‐Bernstam, F., & Gonzalez-Angulo, A. M. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.0766 · Cited by 639 · see citing works
Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor–Positive Breast Cancer
Baselga, J. M., Семиглазов, В. Ф., van Dam, P., Manikhas, A., Bellet, M., Mayordomo, J. I., Campone, M., Kubista, E., Greil, R., Bianchi, G., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.8391 · Cited by 635 · see citing works
mTOR·RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes
Hresko, R. C., & Mueckler, M. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508361200 · Cited by 631 · see citing works
An Emerging Role of mTOR in Lipid Biosynthesis
Laplante, M., & Sabatini, D. M. (2009) · Current Biology · doi:10.1016/j.cub.2009.09.058 · Cited by 614 · see citing works
Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
Franz, D. N., Leonard, J. M., Tudor, C., Chuck, G., Caré, M. M., Sethuraman, G., Dinopoulos, A., Thomas, G., & Crone, K. R. (2006) · Annals of Neurology · doi:10.1002/ana.20784 · Cited by 614 · see citing works
The NF1 tumor suppressor critically regulates TSC2 and mTOR
Johannessen, C. M., Reczek, E. E., James, M. F., Brems, H., Legius, E., & Cichowski, K. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503224102 · Cited by 605 · see citing works
Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer
Thomas, G. V., Tran, C., Mellinghoff, I. K., Welsbie, D. S., Chan, E., Fueger, B., Czernin, J., & Sawyers, C. L. (2006) · Nature Medicine · doi:10.1038/nm1337 · Cited by 604 · see citing works
An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten +/− mice
Podsypanina, K., Lee, R. T., Politis, C., Hennessy, I., Crane, A., Puc, J. A., Neshat, M. S., Wang, H., Yang, L., Gibbons, J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171060098 · Cited by 570 · see citing works
The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations
Huang, C., Mandelker, D. L., Schmidt‐Kittler, O., Samuels, Y., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., Gabelli, S. B., & Amzel, L. M. (2007) · Science · doi:10.1126/science.1150799 · Cited by 564 · see citing works
Increased Activation of the Mammalian Target of Rapamycin Pathway in Liver and Skeletal Muscle of Obese Rats: Possible Involvement in Obesity-Linked Insulin Resistance
Khamzina, L., Veilleux, A., Bergeron, S., & Marette, A. (2005) · Endocrinology · doi:10.1210/en.2004-0921 · Cited by 562 · see citing works
Targeting phosphoinositide 3-kinase—Moving towards therapy
Marone, R., Cmiljanović, V., Giese, B., & Wymann, M. P. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.10.003 · Cited by 548 · see citing works
ATP citrate lyase is an important component of cell growth and transformation
Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208773 · Cited by 537 · see citing works
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
Tabernero, J. M., Rojo, F., Calvo, E., Burris, H. A., Judson, I. R., Hazell, K., Martinelli, E., y Cajal, S. R., Jones, S. F., Vidal, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.5482 · Cited by 537 · see citing works
AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer
Vasudevan, K. M., Barbie, D. A., Davies, M. A., Rabinovsky, R., McNear, C. J., Kim, J. J., Hennessy, B. T., Tseng, H., Pochanard, P., Kim, S. Y., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.04.012 · Cited by 524 · see citing works
Self-citation
Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma
Witzig, T. E., Geyer, S. M., Ghobrial, I. M., Inwards, D. J., Fonseca, R., Kurtin, P. J., Ansell, S. M., Luyun, R. F., Flynn, P. J., Morton, R. F., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.13.466 · Cited by 510 · see citing works
p27 Kip1 modulates cell migration through the regulation of RhoA activationPreprint
Besson, A., Gurian-West, M., Schmidt, A., Hall, A., & Roberts, J. M. (2004) · Genes & Development · doi:10.1101/gad.1185504 · Cited by 487 · see citing works
mTOR Complex1–S6K1 signaling: at the crossroads of obesity, diabetes and cancer
Dann, S. G., Selvaraj, A., & Thomas, G. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.04.002 · Cited by 481 · see citing works
PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP
Porstmann, T., Griffiths, B., Chung, Y.-L., Delpuech, O., Griffiths, J., Downward, J., & Schulze, A. (2005) · Oncogene · doi:10.1038/sj.onc.1208802 · Cited by 479 · see citing works
Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer
Chan, S. Y. T., Scheulen, M. E., Johnston, S. R. D., Mross, K. B., Cardoso, F., Dittrich, C., EIERMANN, W., Hess, D., Morant, R., Семиглазов, В. Ф., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.66.130 · Cited by 468 · see citing works
Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
García‐Martínez, J. M., Moran, J., Clarke, R. G., Gray, A., Cosulich, S. C., Chresta, C. M., & Alessi, D. R. (2009) · Biochemical Journal · doi:10.1042/bj20090489 · Cited by 459 · see citing works
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1
Sofer, A., Lei, K., Johannessen, C. M., & Ellisen, L. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5834-5845.2005 · Cited by 449 · see citing works
mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling
Julien, L.-A., Carriere, A., Moreau, J., & Roux, P. P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00601-09 · Cited by 433 · see citing works
Cancer-specific mutations in PIK3CA are oncogenic in vivo
Bader, A. G., Kang, S., & Vogt, P. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510857103 · Cited by 421 · see citing works
Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1
Dibble, C. C., Asara, J. M., & Manning, B. D. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00735-09 · Cited by 420 · see citing works
Inhibition of mTOR Activity Restores Tamoxifen Response in Breast Cancer Cells with Aberrant Akt Activity
deGraffenried, L. A., Friedrichs, W. E., Russell, D. H., Donzis, E. J., Middleton, A. K., Silva-Fisher, J., Roth, R. A., & Hidalgo, M. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0035 · Cited by 387 · see citing works
The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes
Berwick, D. C., Hers, I., Heesom, K. J., Moule, S. K., & Tavareá, J. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204681200 · Cited by 383 · see citing works
PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR
Zhang, H., Bajraszewski, N., Wu, E., Wang, H., Moseman, A. P., Dabora, S. L., Griffin, J. D., & Kwiatkowski, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28984 · Cited by 382 · see citing works
Oncogenic B-RAF Negatively Regulates the Tumor Suppressor LKB1 to Promote Melanoma Cell Proliferation
Zheng, B., Jeong, J. H., Asara, J. M., Yuan, Y.-Y., Granter, S. R., Chin, L., & Cantley, L. C. (2009) · Molecular Cell · doi:10.1016/j.molcel.2008.12.026 · Cited by 359 · see citing works
Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus
Nicolantonio, F. D., Arena, S., Tabernero, J. M., Grosso, S., Molinari, F., Macarulla, T. M., Russo, M., Cancelliere, C., Zecchin, D., Mazzucchelli, L., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci37539 · Cited by 343 · see citing works
Oncogenic MAPK Signaling Stimulates mTORC1 Activity by Promoting RSK-Mediated Raptor Phosphorylation
Carrière, A., Cargnello, M., Julien, L.-A., Gao, H., Bonneil, É., Thibault, P., & Roux, P. P. (2008) · Current Biology · doi:10.1016/j.cub.2008.07.078 · Cited by 332 · see citing works
Biochemical, Cellular, and In vivo Activity of Novel ATP-Competitive and Selective Inhibitors of the Mammalian Target of Rapamycin
Yu, K., Toral‐Barza, L., Shi, C., Zhang, W., Lucas, J., Shor, B., Kim, J., Verheijen, J. C., Curran, K. J., Malwitz, D. J., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0299 · Cited by 332 · see citing works
Targeting the mTOR signaling network in cancer
Chiang, G. G., & Abraham, R. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.08.001 · Cited by 328 · see citing works
Common corruption of the mTOR signaling network in human tumors
Menon, S., & Manning, B. D. (2008) · Oncogene · doi:10.1038/onc.2009.352 · Cited by 328 · see citing works
Targeting Mammalian Target of Rapamycin Synergistically Enhances Chemotherapy-Induced Cytotoxicity in Breast Cancer Cells
Mondesire, W. H., Jian, W., Zhang, H., Ensor, J., Hung, M., Mills, G. B., & Meric‐Bernstam, F. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0361 · Cited by 319 · see citing works
A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas
Durán, I., Kortmansky, J. S., Singh, D., Hirte, H. W., Kocha, W., Goss, G. D., Le, L., Oza, A. M., Nicklee, T., Ho, J., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603419 · Cited by 318 · see citing works
Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells
Brachmann, S. M., Hofmann, I., Schnell, C., Fritsch, C. M., Wee, S., Lane, H. A., Wang, S., Garcı́a-Echeverrı́a, C., & Maira, S.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905152106 · Cited by 299 · see citing works
Determinants of Rapamycin Sensitivity in Breast Cancer Cells
Noh, W.-C., Mondesire, W. H., Peng, J., Jian, W., Zhang, H., Dong, J., Mills, G. B., Hung, M., & Meric‐Bernstam, F. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0043 · Cited by 286 · see citing works
Phase I/II Study of the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) in Patients with Relapsed or Refractory Hematologic Malignancies
Yee, K. W. L., Zeng, Z., Konopleva, M. Y., Verstovšek, S., Ravandi, F., Ferrajoli, A., Thomas, D. A., Wierda, W. G., Apostolidou, E., Albitar, M. X., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0764 · Cited by 283 · see citing works
A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma
Slomovitz, B. M., Lu, K. H., Johnston, T., Coleman, R. L., Munsell, M. F., Broaddus, R. R., Walker, C., Ramondetta, L. M., Burke, T. W., Gershenson, D. M., et al. (2010) · Cancer · doi:10.1002/cncr.25515 · Cited by 270 · see citing works
Randomized Phase II Study Comparing Two Schedules of Everolimus in Patients With Recurrent/Metastatic Breast Cancer: NCIC Clinical Trials Group IND.163
Ellard, S. L., Clemons, M. J., Gelmon, K. A., Norris, B. D., Kennecke, H. F., Chia, S., Pritchard, K. I., Eisen, A. F., Vandenberg, T. A., Taylor, M., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.3033 · Cited by 259 · see citing works
NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas
Liu, T.-J., Koul, D., LaFortune, T. A., Tiao, N., Shen, R., Maira, S.-M., Garcia-Echevrria, C., & Yung, W. K. A. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0160 · Cited by 254 · see citing works
mTOR-Raptor Binds and Activates SGK1 to Regulate p27 Phosphorylation
Hong, F., Larrea, M. D., Doughty, C. A., Kwiatkowski, D. J., Squillace, R. M., & Slingerland, J. M. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.027 · Cited by 252 · see citing works
Self-citation
Spectrum of Phosphatidylinositol 3-Kinase Pathway Gene Alterations in Bladder Cancer
Platt, F. M., Hurst, C. D., Taylor, C., Gregory, W. M., Harnden, P., & Knowles, M. A. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0898 · Cited by 249 · see citing works
Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779.
Shi, Y., Gera, J., Hu, L., Hsu, J.-H., Bookstein, R., Li, W., & Lichtenstein, A. K. (2002) · PubMed · Cited by 232 · see citing works
CCI‐779 in metastatic melanoma
Margolin, K. A., Longmate, J., Baratta, T., Synold, T. W., Christensen, S., Weber, J. S., Gajewski, T. F., Quirt, I. C., & Doroshow, J. H. (2005) · Cancer · doi:10.1002/cncr.21265 · Cited by 228 · see citing works
Not all substrates are treated equally: Implications for mTOR, rapamycin-resistance, and cancer therapy
Choo, A. Y., & Blenis, J. (2009) · Cell Cycle · doi:10.4161/cc.8.4.7659 · Cited by 213 · see citing works
A Phase I and Pharmacokinetic Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients with Advanced Cancer
Hidalgo, M. M., Buckner, J. C., Erlichman, C., Pollack, M. S., Boni, J. P., Dukart, G., Marshall, B., Speicher, L. A., Moore, L., & Rowinsky, E. K. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0118 · Cited by 212 · see citing works
Phosphorylation of p27Kip1 at Threonine 198 by p90 Ribosomal Protein S6 Kinases Promotes Its Binding to 14-3-3 and Cytoplasmic Localization
Fujita, N., Sato, S., & Tsuruo, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306614200 · Cited by 210 · see citing works
Low‐dose, single‐agent temsirolimus for relapsed mantle cell lymphoma
Ansell, S. M., Inwards, D. J., Rowland, K. M., Flynn, P. J., Morton, R. F., Moore, D. F., Kaufmann, S. H., Ghobrial, I. M., Kurtin, P. J., Maurer, M. J., et al. (2008) · Cancer · doi:10.1002/cncr.23580 · Cited by 203 · see citing works
Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium
Smith, S. M., van Besien, K., Karrison, T. G., Dancey, J. E., McLaughlin, P. J., Younes, A., Smith, S. E., Stiff, P. J., Lester, E. P., Modi, S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.2813 · Cited by 203 · see citing works
The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell Carcinoma
Cho, D. C., Cohen, M. B., Panka, D. J., Collins, M. P., Ghebremichael, M. S., Atkins, M. B., Signoretti, S., & Mier, J. W. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3022 · Cited by 190 · see citing works
PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML
Park, S., Chapuis, N., Bardet, V., Tamburini, J., Gallay, N., Willems, L., Knight, Z. A., Shokat, K. M., Azar, N., Viguié, F., et al. (2008) · Leukemia · doi:10.1038/leu.2008.144 · Cited by 189 · see citing works
BRAF as therapeutic target in melanoma
Wellbrock, C., & Hurlstone, A. F. L. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.03.019 · Cited by 178 · see citing works
Potential Histologic and Molecular Predictors of Response to Temsirolimus in Patients with Advanced Renal Cell Carcinoma
Cho, D., Signoretti, S., Dabora, S. L., Regan, M. M., Seeley, A., Mariotti, M., Youmans, A. J., Polivy, A., Mandato, L., McDermott, D. F., et al. (2007) · Clinical Genitourinary Cancer · doi:10.3816/cgc.2007.n.020 · Cited by 178 · see citing works
Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway
deGraffenried, L. A., Fulcher, L. C., Friedrichs, W. E., Grünwald, V., Ray, R. B., & Hidalgo, M. M. (2004) · Annals of Oncology · doi:10.1093/annonc/mdh388 · Cited by 177 · see citing works
Serum and glucocorticoid‐regulated protein kinases: Variations on a theme
Tessier, M., & Woodgett, J. R. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20894 · Cited by 175 · see citing works
Effects of the Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 on the Tumor Vasculature: Implications for Clinical Imaging
Schnell, C., Stauffer, F., ALLEGRINI, P. R., O’Reilly, T., McSheehy, P. M. J., Dartois, C., Stumm, M., Cozens, R. M., Littlewood-Evans, A. J., Garcia-Echeverria, C., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1044 · Cited by 175 · see citing works
Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors
Kevin, M. C. (2001) · Frontiers in bioscience · doi:10.2741/coleman · Cited by 174 · see citing works
Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors
Steelman, L. S., Navolanic, P. M., Sokolosky, M. L., Taylor, J. R., Lehmann, B. D., Chappell, W. H., Abrams, S. L., Wong, E. W. T., Stadelman, K. M., Terrian, D. M., et al. (2008) · Oncogene · doi:10.1038/onc.2008.49 · Cited by 170 · see citing works
Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling
Beeram, M., Tan, Q.-T. N., Tekmal, R., Russell, D., Middleton, A. K., & deGraffenried, L. A. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm170 · Cited by 170 · see citing works
Status of PI3K inhibition and biomarker development in cancer therapeutics
Markman, B., Atzori, F., Pérez-García, J. M., Tabernero, J. M., & Baselga, J. M. (2009) · Annals of Oncology · doi:10.1093/annonc/mdp347 · Cited by 159 · see citing works
Targeting mTOR globally in cancer: Thinking beyond rapamycin
Shor, B., Gibbons, J. J., Abraham, R. T., & Yu, K. (2009) · Cell Cycle · doi:10.4161/cc.8.23.10070 · Cited by 156 · see citing works
The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: Results of a phase I study with pharmacokinetics
Awada, A. H., Cardoso, F., Fontaine, C., Dirix, L. Y., Grève, J. D., Sotiriou, C. P., Steinseifer, J., Wouters, C., Tanaka, C., Zoellner, U., et al. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.10.003 · Cited by 149 · see citing works
RSK1 drives p27 Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility
Larrea, M. D., Hong, F., Wander, S. A., Silva, T. G. D., Helfman, D. M., Lannigan, D. A., Smith, J. A., & Slingerland, J. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805057106 · Cited by 147 · see citing works
Self-citation
Phospho-S6 ribosomal protein: a potential new predictive sarcoma marker for targeted mTOR therapy
Iwenofu, O., Lackman, R., Staddon, A., Goodwin, D., Haupt, H. M., & Brooks, J. (2008) · Modern Pathology · doi:10.1038/modpathol.3800995 · Cited by 138 · see citing works
Human cancers converge at the HIF-2α oncogenic axis
Franovic, A., Holterman, C. E., Payette, J., & Lee, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906432106 · Cited by 128 · see citing works
Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts
Cao, P., Maira, S.-M., Garcı́a-Echeverrı́a, C., & Hedley, D. W. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604995 · Cited by 125 · see citing works
Antimyeloma Activity of the Orally Bioavailable Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235
McMillin, D. W., Ooi, M. G. M., Delmore, J. E., Negri, J. M., Hayden, P. J., Mitsiades, N., Jakubı́ková, J., Maira, S.-M., Garcı́a-Echeverrı́a, C., Schlossman, R. L., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4285 · Cited by 124 · see citing works
Mutation of the 9q34 gene TSC1 in sporadic bladder cancer
Hornigold, N., Devlin, J., Davies, A. M., Aveyard, J. S., Habuchi, T., & Knowles, M. A. (1999) · Oncogene · doi:10.1038/sj.onc.1202854 · Cited by 123 · see citing works
Targeting Melanoma with Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors
Marone, R., Erhart, D., Mertz, A. C., Bohnacker, T., Schnell, C., Cmiljanović, V., Stauffer, F., Garcı́a-Echeverrı́a, C., Giese, B., Maira, S.-M., et al. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0366 · Cited by 121 · see citing works
Antitumoral Activity of Rapamycin in Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex
Wienecke, R., Fackler, I., Linsenmaier, U., Mayer, K., Licht, T., & Kretzler, M. (2006) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.05.018 · Cited by 119 · see citing works
Uncoupling of the LKB1-AMPKα Energy Sensor Pathway by Growth Factors and Oncogenic BRAFV600E
Esteve‐Puig, R., Canals, F., Colomé, N., Merlino, G. T., & Recio, J. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004771 · Cited by 115 · see citing works
Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder.
Knowles, M. A., Habuchi, T., Kennedy, W., & Cuthbert-Heavens, D. (2003) · PubMed · Cited by 111 · see citing works
Relocalized p27Kip1 Tumor Suppressor Functions as a Cytoplasmic Metastatic Oncogene in Melanoma
Denicourt, C., Saenz, C. C., Datnow, B., Cui, X.-S., & Dowdy, S. F. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1375 · Cited by 111 · see citing works
Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability
Xue, Q., Hopkins, B. D., Perruzzi, C. A., Udayakumar, D., Sherris, D., & Benjamin, L. E. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2058 · Cited by 109 · see citing works
First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Burris, H. A., Rodon, J. A., Sharma, S., Herbst, R. S., Tabernero, J. M., Infante, J. R., Silva, A. M. E., Demanse, D., Hackl, W., & Baselga, J. M. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3005 · Cited by 109 · see citing works
A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer
Colombo, N., McMeekin, S., Schwartz, P. E., Kostka, J., Sessa, C., Gehrig, P. A., Holloway, R., Braly, P. S., Matei, D. E., & Einstein, M. H. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.5516 · Cited by 100 · see citing works
Tuberin and hamartin are aberrantly expressed and linked to clinical outcome in human breast cancer: The role of promoter methylation of TSC genes
Jiang, W. G., Sampson, J. R., Martin, T. A., Lee‐Jones, L., Watkins, G., Douglas-Jones, A. G., Mokbel, K., & Mansel, R. E. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.03.023 · Cited by 99 · see citing works
Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma
Chakraborty, S., Mohiyuddin, S. M. A., Gopinath, K., & Kumar, A. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-163 · Cited by 99 · see citing works
C‐terminal phosphorylation controls the stability and function of p27kip1
Kossatz-Boehlert, U., Vervoorts, J., Nickeleit, I., Sundberg, H. A., Arthur, J. S. C., Manns, M. P., & Malek, N. P. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601388 · Cited by 79 · see citing works
Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous sclerosis complex
Herry, I., Neukirch, C., Debray, M., Mignon, F., & Crestani, B. (2007) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2006.07.017 · Cited by 75 · see citing works
Updated results of a phase II trial of AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas
Chawla, S. P., Tolcher, A. W., Staddon, A. P., Schuetze, S. M., D’Amato, G. Z., Blay, J., Sankhala, K. K., Daly, S. T., Rivera, V. M., & Demetri, G. D. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.9505 · Cited by 74 · see citing works
Akt-Dependent T198 Phosphorylation of Cyclin-Dependent Kinase Inhibitor p27kip1in Breast Cancer
Motti, M. L., Marco, C. D., Califano, D., Fusco, A., & Viglietto, G. (2004) · Cell Cycle · doi:10.4161/cc.3.8.1073 · Cited by 67 · see citing works
Antitumor Efficacy Profile of PKI-402, a Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor
Mallon, R. G., Hollander, I. J., Feldberg, L. R., Lucas, J., Soloveva, V., Venkatesan, A. M., Dehnhardt, C. M., Santos, E. D., Chen, Z., dos Santos, O., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0954 · Cited by 65 · see citing works
Pulmonary lymphangioleiomyomatosis (LAM): Progress and current challenges
Goncharova, E. A., & Krymskaya, V. P. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21419 · Cited by 53 · see citing works
A phase I study of temsirolimus and metformin in advanced solid tumours
MacKenzie, M. J., Ernst, S., Johnson, C., & Winquist, E. (2010) · Investigational New Drugs · doi:10.1007/s10637-010-9570-8 · Cited by 53 · see citing works
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765 (SAR245409), a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced malignancies.
Braña, I., LoRusso, P. M., Baselga, J. M., Heath, E. I., Patnaik, A., Gendreau, S., Laird, A., & Papadopoulos, K. P. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3030 · Cited by 51 · see citing works
First-in-human phase I study exploring three schedules of OSI-027, a novel small molecule TORC1/TORC2 inhibitor, in patients with advanced solid tumors and lymphoma.
Tan, D. S.-W., Dumez, H., Olmos, D., Sandhu, S. K., Hoeben, A., Stephens, A. W., Poondru, S., Gedrich, R. W., Kaye, S. B., & Schöffski, P. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3006 · Cited by 50 · see citing works
Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas
Wienecke, R., Guha, A., Maize, J. C., Heideman, R. L., DeClue, J. E., & Gutmann, D. H. (1997) · Annals of Neurology · doi:10.1002/ana.410420215 · Cited by 44 · see citing works
A phase II study of oral mammalian target of rapamycin (mTOR) inhibitor, RAD001 (everolimus), in patients with recurrent endometrial carcinoma (EC)
Slomovitz, B. M., Lu, K. H., Johnston, T., Munsell, M. A., Ramondetta, L. M., Broaddus, R. R., Coleman, R. L., Walker, C., Gershenson, D. M., Burke, T. W., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.5502 · Cited by 39 · see citing works
Combination therapy for treating breast cancer using antiestrogen, ERA-923, and the mammalian target of rapamycin inhibitor, temsirolimus
Sadler, T., Gavriil, M., Annable, T., Frost, P., Greenberger, L. M., & Zhang, Y. (2006) · Endocrine Related Cancer · doi:10.1677/erc.1.01170 · Cited by 38 · see citing works
Aberrant expression of TSC2 gene in the newly diagnosed acute leukemia
Xu, Z., Wang, M., Wang, L., Wang, Y., Zhao, X., Rao, Q., & Wang, J. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.01.041 · Cited by 37 · see citing works
Activity of single agent temsirolimus (CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes
Smith, S. M., Pro, B., Cisneros, A., Smith, S. E., Stiff, P. J., Lester, E. P., Modi, S., Dancey, J. E., Vokes, E. E., & van Besien, K. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.8514 · Cited by 33 · see citing works
Phase III study of patients with relapsed, refractory mantle cell lymphoma treated with temsirolimus compared with investigator’s choice therapy
Hess, G., Romaguera, J. E., Verhoef, G. E. G., Herbrecht, R., Crump, M., Strahs, A. L., Clancy, J. S., Hewes, B., & Coiffier, B. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.8513 · Cited by 27 · see citing works
Denicourt, C., Saenz, C. C., Datnow, B., Cui, X. S. & Dowdy, S. F. Relocalized p27KiP1 tumor suppressor functions as a cytoplasmic metastatic oncogene in melanoma. Cancer Res. 67, 9238-9243
Denicourt, C., Saenz, C. C., Datnow, B., Cui, X.-S., & Dowdy, S. F. (2007) · Cited by 23 · see citing works
Maintenance with everolimus (RAD001) and trastuzumab (T) after discontinuation of chemotherapy in patients (pts) with heavily pretreated HER2-positive metastatic breast cancer (MBC): Pooled data of extension cohorts of phase Ib/II studies.
Jérusalem, G., Fasolo, A., Massacesi, C., Balaisius, M., Manlius, C., Sahmoud, T., André, F., & Gianni, L. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.1041 · Cited by 13 · see citing works
Everolimus for subependymal giant-cell astrocytomas (SEGAs) in tuberous sclerosis (TS).
Franz, D. N., Krueger, D. A., Caré, M. M., Holland‐Bouley, K. D., Agricola, K. D., Tudor, C., Mangeshkar, P., Byars, A. W., & Sahmoud, T. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.2004 · Cited by 10 · see citing works

Flagged first, then by citations

1 of the 157 references couldn’t be matched to a known paper.

Research works printed but not linked: 5

Frodin M, Gammeltoft S. Role and regula- tion of 90kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol. 1999; 151(1-2):65-77.
Goncharova EA, Krymskaya VP. Pulmonary lymphan- gioleiomyomatosis (LAM): progress and current chal- lenges. J Cell Biochem. 2008;103(2):369-382.
Huang CH, et al. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science. 2007; 318(5857):1744-1748.
Esteve-Puig R, Canals F, Colome N, Merlino G, Recio JA. Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and onco- genic BRAF. PLoS One. 2009;4(3):e4771.
Meric-Bernstam F, Gonzalez-Angulo AM. Target- ing the mTOR signaling network for cancer thera- py. J Clin Oncol. 2009;27(13):2278-2287.

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Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
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Rodon, J. A., Dienstmann, R., Serra, V., & Tabernero, J. M. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.10 · Cited by 770 · see citing works
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Costa, R. L. B., Shah, A. N., Santa-Maria, C. A., Cruz, M. R. D. S., Mahalingam, D., Carneiro, B. A., Chae, Y. K., Cristofanilli, M., Gradishar, W. J., & Giles, F. J. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.12.010 · Cited by 176 · see citing works
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Self-citation
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Self-citation
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Wang, C., Cigliano, A., Delogu, S., Armbruster, J., Dombrowski, F., Evert, M., Chen, X., & Calvisi, D. F. (2013) · Cell Cycle · doi:10.4161/cc.25099 · Cited by 92 · see citing works
ATG4B promotes colorectal cancer growth independent of autophagic flux
Liu, P., Leung, C., Chang, Y.-H., Cheng, J., Chen, J., Weng, C.-J., Tsai, K., Hsu, C.-J., Liu, Y., Hsu, P., et al. (2014) · Autophagy · doi:10.4161/auto.29556 · Cited by 89 · see citing works
Controversies around the function of LARP1
Berman, A. J., Thoreen, C. C., Dedeić, Z., Chettle, J., Roux, P. P., & Blagden, S. P. (2020) · RNA Biology · doi:10.1080/15476286.2020.1733787 · Cited by 79 · see citing works
Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer
Treilleux, I., Arnedos, M., Cropet, C., Wang, Q., Ferrero, J.-M., Abadie‐Lacourtoisie, S., Lévy, C., Legouffe, É., Lortholary, A. H., Pujade-Lauraine, É., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu497 · Cited by 85 · see citing works
Regulation of Blood–Testis Barrier (BTB) Dynamics during Spermatogenesis via the “Yin” and “Yang” Effects of Mammalian Target of Rapamycin Complex 1 (mTORC1) and mTORC2
Mok, K., Mruk, D. D., & Cheng, C. Y. (2013) · International review of cytology · doi:10.1016/b978-0-12-407704-1.00006-3 · Cited by 82 · see citing works
4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N‐Ras proto‐oncogenes in mice
Wang, C., Cigliano, A., Jiang, L., Li, X., Fan, B., Pilo, M. G., Liu, Y., Gui, B., Sini, M., Smith, J. W., et al. (2014) · Hepatology · doi:10.1002/hep.27396 · Cited by 83 · see citing works
Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant Patients Treated with mTOR Inhibitors
Zaza, G., Tomei, P., Ria, P., Granata, S., Boschiero, L., & Lupo, A. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/403280 · Cited by 83 · see citing works
Everolimus in the Treatment of Metastatic Breast Cancer
Royce, M., & Osman, D. I. (2015) · Breast Cancer Basic and Clinical Research · doi:10.4137/bcbcr.s29268 · Cited by 82 · see citing works
4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer
Wang, Z., Feng, X., Molinolo, A., Martı́n, D., Vitale-Cross, L. A., Nohata, N., Ando, M., Wahba, A., Amornphimoltham, P., Wu, X., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-1220 · Cited by 79 · see citing works
Inhibition of mTOR complex 1/p70 S6 kinase signaling elevates PD-L1 levels in human cancer cells through enhancing protein stabilization accompanied with enhanced β-TrCP degradation
Deng, L. H., Qian, G., Zhang, S., Zheng, H., Fan, S., Lesinski, G. B., Owonikoko, T. K., Ramalingam, S. S., & Sun, S. (2019) · Oncogene · doi:10.1038/s41388-019-0877-4 · Cited by 82 · see citing works
mTORC1‐ and mTORC2‐interacting proteins keep their multifunctional partners focused
Bracho‐Valdés, I., Moreno‐Alvarez, P., Valencia‐Martínez, I., Robles‐Molina, E., Chávez‐Vargas, L., & Vázquez‐Prado, J. (2011) · IUBMB Life · doi:10.1002/iub.558 · Cited by 81 · see citing works
Conditional Disruption of Raptor Reveals an Essential Role for mTORC1 in B Cell Development, Survival, and Metabolism
Iwata, T., Ramírez, J. A., Tsang, M., Park, H., Margineantu, D. H., Hockenbery, D. M., & Iritani, B. M. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600492 · Cited by 82 · see citing works
Mammalian Target of Rapamycin Inhibitor-Associated Stomatitis
Boers-Doets, C. B., Raber‐Durlacher, J. E., Treister, N. S., Epstein, J. B., Arends, A. B., Wiersma, D. R., Lalla, R. V., Logan, R. M., van Erp, N. P., & Gelderblom, H. A. J. (2013) · Future Oncology · doi:10.2217/fon.13.141 · Cited by 81 · see citing works
Investigational drug MLN0128, a novel TORC1/2 inhibitor, demonstrates potent oral antitumor activity in human breast cancer xenograft models
Gökmen‐Polar, Y., Liu, Y., Toroni, R. A., Sanders, K. L., Mehta, R. J., Badve, S., Rommel, C., & Sledge, G. W. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2298-8 · Cited by 79 · see citing works
Autophagy in Pulmonary Diseases
Nakahira, K., Pabon Porras, M. A., & Choi, A. M. K. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2468so · Cited by 78 · see citing works
Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas
Khan, T., Relitti, N., Brindisi, M., Magnano, S., Zisterer, D. M., Gemma, S., Butini, S., & Campiani, G. (2019) · Medicinal Research Reviews · doi:10.1002/med.21646 · Cited by 78 · see citing works
mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition
Limon, J. J., So, L., Jellbauer, S., Chiu, H., Corado, J., Sykes, S. M., Raffatellu, M., & Fruman, D. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407104111 · Cited by 76 · see citing works
mTOR co-targeting strategies for head and neck cancer therapy
Wang, Z., Valera, J. L. C., Zhao, X., Chen, Q., & Gutkind, J. S. (2017) · Cancer and Metastasis Reviews · doi:10.1007/s10555-017-9688-7 · Cited by 76 · see citing works
Dueling for dual inhibition: Means to enhance effectiveness of PI3K/Akt/mTOR inhibitors in AML
Herschbein, L., & Liesveld, J. L. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.11.006 · Cited by 76 · see citing works
Clinical management of obese patients with cancer
Tao, W., & Lagergren, J. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.120 · Cited by 75 · see citing works
Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy
Johnson, S. A., & Spurney, R. F. (2015) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00266.2015 · Cited by 75 · see citing works
The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence
Lahr, R. M., Mack, S. M., Heroux, A., Blagden, S. P., Bousquet‐Antonelli, C., Deragon, J., & Berman, A. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv748 · Cited by 74 · see citing works

Authors: Wander, S. A., Hennessy, B. T., & Slingerland, J. M.
Affiliations: University of Miami (US)
Royal College of Surgeons in Ireland (IE)
Corresponding author: Slingerland, Joyce M.
ORCID: Wander, Seth A.
Hennessy, Bryan T.
Slingerland, Joyce M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2011-04-01
Volume: 121
Issue: 4
Pages: 1231-1241
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci44145
PMC: PMC3069769
OpenAlex: W2025935112
Cited by: 427
References: 157
Citations by year: 2026: 7 · 2025: 17 · 2024: 10 · 2023: 18 · 2022: 16 · 2021: 14 · 2020: 23 · 2019: 23 · 2018: 27 · 2017: 39 · 2016: 28 · 2015: 63 · 2014: 51 · 2013: 47 · 2012: 28
FWCI: 4.09
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
Funders: Doris Duke Charitable Foundation
National Institutes of Health (5-R01-)
National Cancer Institute (5-R01-CA-105118-04, R01CA105118)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: mTOR inhibitors, mTOR signaling, mTORC1, mTORC2, PI3K-related kinases, cancer therapy, therapeutic target
MeSH terms: Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Phosphoinositide-3 Kinase Inhibitors, Antineoplastic Agents, Clinical Trials as Topic, Female, Humans, Male, Neoplasms, Transcription Factors, Signal Transduction, Phosphatidylinositol 3-Kinases, Sirolimus, Tumor Suppressor Proteins, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases

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Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

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