ATP-competitive inhibitors of mTOR: New perspectives in the treatment of renal cell carcinoma

Biochemical Society Transactions

Volumn 39, Issue 2, 2011, Pages 492-494

  Roulin, Didier ^a   Demartines, Nicolas ^a   Dormond, Olivier ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

ATP competitive inhibitor; Hypoxia inducible factor (HIF); Mammalian target of rapamycin (mTOR); Rapalogue; Renal cell carcinoma (RCC)

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; ADENOSINE TRIPHOSPHATE; ALPHA INTERFERON; EVEROLIMUS; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PAZOPANIB; PLACEBO; RAPAMYCIN; RAPAMYCIN DERIVATIVE; SORAFENIB; SUNITINIB; TEMSIROLIMUS; UNCLASSIFIED DRUG; VASCULOTROPIN; VON HIPPEL LINDAU PROTEIN; WYE 123; WYE 132;

ANTINEOPLASTIC ACTIVITY; CARCINOGENESIS; DISEASE ASSOCIATION; DRUG MECHANISM; GLIOMA; HUMAN; KIDNEY CARCINOMA; MEDICAL LITERATURE; MELANOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW;

ADENOSINE TRIPHOSPHATE; ANIMALS; BINDING, COMPETITIVE; CARCINOMA, RENAL CELL; DRUGS, INVESTIGATIONAL; HUMANS; KIDNEY NEOPLASMS; PROTEIN KINASE INHIBITORS; TOR SERINE-THREONINE KINASES;

MAMMALIA;

EID: 79953208697     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST0390492     Document Type: Review

References (34)

1. Cohen, H.T. and McGovern, F.J. (2005) Renal-cell carcinoma. N. Engl. J. Med. 353, 2477-2490
2. Rini, B.I., Campbell, S.C. and Escudier, B. (2009) Renal cell carcinoma. Lancet 373, 1119-1132
3. Kaelin, Jr, W.G. (2009) Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 115, 2262-2272
4. Flaherty, K.T. and Puzanov, I. (2010) Building on a foundation of VEGF and mTOR targeted agents in renal cell carcinoma. Biochem. Pharmacol. 80, 638-646
5. Kim, W.Y. and Kaelin, W.G. (2004) Role of VHL gene mutation in human cancer. J. Clin. Oncol. 22, 4991-5004
6. Iliopoulos, O., Kibel, A., Gray, S. and Kaelin, Jr, W.G. (1995) Tumour suppression by the human von Hippel-Lindau gene product. Nat. Med. 1, 822-826
7. 2 sensing and cancer. Nat. Rev. Cancer 8, 865-873
8. Semenza, G.L. (2003) Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3, 721-732
9. Kondo, K., Kim, W.Y., Lechpammer, M. and Kaelin, Jr, W.G. (2003) Inhibition of HIF2á is sufficient to suppress pVHL-defective tumor growth. PLoS Biol. 1, E83
10. Kondo, K., Klco, J., Nakamura, E., Lechpammer, M. and Kaelin, Jr, W.G. (2002) Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1, 237-246
11. Dasanu, C.A., Clark, III, B.A. and Alexandrescu, D.T. (2009) mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option. Expert Opin. Invest. Drugs 18, 175-187
12. Wullschleger, S., Loewith, R. and Hall, M.N. (2006) TOR signaling in growth and metabolism. Cell 124, 471-484
13. Guertin, D.A. and Sabatini, D.M. (2009) The pharmacology of mTOR inhibition. Sci. Signaling 2, pe24
14. Sarbassov, D.D., Ali, S.M., Sengupta, S., Sheen, J.H., Hsu, P.P., Bagley, A.F., Markhard, A.L. and Sabatini, D.M. (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 22, 159-168
15. Efeyan, A. and Sabatini, D.M. mTOR and cancer: many loops in one pathway. Curr. Opin. Cell Biol. 22, 169-176
16. Guba, M., von Breitenbuch, P., Steinbauer, M., Koehl, G., Flegel, S., Hornung, M., Bruns, C.J., Zuelke, C., Farkas, S., Anthuber, M. et al. (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat. Med. 8, 128-135
17. Hudes, G., Carducci, M., Tomczak, P., Dutcher, J., Figlin, R., Kapoor, A., Staroslawska, E., Sosman, J., McDermott, D., Bodrogi, I. et al. (2007) Temsirolimus, interferon α, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356, 2271-2281
18. Motzer, R.J., Escudier, B., Oudard, S., Hutson, T.E., Porta, C., Bracarda, S., Grunwald, V., Thompson, J.A., Figlin, R.A., Hollaender, N. et al. (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372, 449-456
19. Faivre, S. and Raymond, E. (2008) Mechanism of action of rapalogues: the antiangiogenic hypothesis. Expert Opin. Invest. Drugs 17, 1619-1621
20. Hudson, C.C., Liu, M., Chiang, G.G., Otterness, D.M., Loomis, D.C., Kaper, F., Giaccia, A.J. and Abraham, R.T. (2002) Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 22, 7004-7014
21. Dormond, O., Madsen, J.C. and Briscoe, D.M. (2007) The effects of mTOR-Akt interactions on anti-apoptotic signaling in vascular endothelial cells. J. Biol. Chem. 282, 23679-23686
22. Shiojima, I. and Walsh, K. (2002) Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res. 90, 1243-1250
23. Velickovic, M., Delahunt, B., McIver, B. and Grebe, S.K. (2002) Intragenic PTEN/MMAC1 loss of heterozygosity in conventional (clear-cell) renal cell carcinoma is associated with poor patient prognosis. Mod. Pathol. 15, 479-485
24. Hara, S., Oya, M., Mizuno, R., Horiguchi, A., Marumo, K. and Murai, M. (2005) Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor. Ann. Oncol. 16, 928-933
25. Cho, D.C., Cohen, M.B., Panka, D.J., Collins, M., Ghebremichael, M., Atkins, M.B., Signoretti, S. and Mier, J.W. (2010) The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin. Cancer Res. 16, 3628-3638
26. Tabernero, J., Rojo, F., Calvo, E., Burris, H., Judson, I., Hazell, K., Martinelli, E., Ramon y Cajal, S., Jones, S., Vidal, L. et al. (2008) Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J. Clin. Oncol. 26, 1603-1610
27. García-Echeverría, C. (2010) Allosteric and ATP-competitive kinase inhibitors of mTOR for cancer treatment. Bioorg. Med. Chem. Lett. 20, 4308-4312
28. Albert, S., Serova, M., Dreyer, C., Sablin, M.P., Faivre, S. and Raymond, E. (2010) New inhibitors of the mammalian target of rapamycin signaling pathway for cancer. Expert Opin. Invest. Drugs 19, 919-930
29. Sourbier, C., Lindner, V., Lang, H., Agouni, A., Schordan, E., Danilin, S., Rothhut, S., Jacqmin, D., Helwig, J.J. and Massfelder, T. (2006) The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Cancer Res. 66, 5130-5142 (Pubitemid 43844935)
30. Cao, P., Maira, S.M., García-Echeverría, C. and Hedley, D.W. (2009) Activity of a novel, dual PI3-kinase/mTOR inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts. Br. J. Cancer 100, 1267-1276
31. Marone, R., Erhart, D., Mertz, A.C., Bohnacker, T., Schnell, C., Cmiljanovic, V., Stauffer, F., García-Echeverría, C., Giese, B., Maira, S.M. and Wymann, M.P. (2009) Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol. Cancer Res. 7, 601-613
32. Liu, T.J., Koul, D., LaFortune, T., Tiao, N., Shen, R.J., Maira, S.M., García-Echeverría, C. and Yung, W.K. (2009) NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas. Mol. Cancer Ther. 8, 2204-2210
33. Yuan, T.L., Choi, H.S., Matsui, A., Benes, C., Lifshits, E., Luo, J., Frangioni, J.V. and Cantley, L.C. (2008) Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 105, 9739-9744
34. Yu, K., Shi, C., Toral-Barza, L., Lucas, J., Shor, B., Kim, J.E., Zhang, W.G., Mahoney, R., Gaydos, C., Tardio, L. et al. (2010) Beyond rapalogue therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res. 70, 621-631