Targeting the PI3K-Akt pathway in human cancer: Rationale and promise

Cancer Cell

Volumn 4, Issue 4, 2003, Pages 257-262

  Luo, Ji ^a,b   Manning, Brendan D ^b   Cantley, Lewis C ^b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 7 HYDROXYSTAUROSPORINE; ANTINEOPLASTIC AGENT; EVEROLIMUS; HAMARTIN; IMATINIB; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN BAD; PROTEIN KINASE B; RAPAMYCIN; SR 13668; SR 3668; TEMSIROLIMUS; TRASTUZUMAB; TUBERIN; UC 01; UNCLASSIFIED DRUG; WORTMANNIN;

APOPTOSIS; CANCER; CANCER GENETICS; CARCINOGENESIS; CELL FUNCTION; CELL SURVIVAL; HUMAN; NONHUMAN; OVARY TUMOR; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

EID: 0142227019     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1535-6108(03)00248-4     Document Type: Review

References (64)

1. Barnes D.M., Gillett C.E. Cyclin D1 in breast cancer. Breast Cancer Res. Treat. 52:1998;1-15.
2. Bellacosa A., Testa J.R., Staal S.P., Tsichlis P.N. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science. 254:1991;274-277.
3. Bianco R., Shin I., Ritter C.A., Yakes F.M., Basso A., Rosen N., Tsurutani J., Dennis P.A., Mills G.B., Arteaga C.L. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene. 22:2003;2812-2822.
4. Burgering B.M., Medema R.H. Decisions on life and death. FOXO Forkhead transcription factors are in command when PKB/Akt is off duty J. Leukoc. Biol. 73:2003;689-701.
5. Cantley L.C. The phosphoinositide 3-kinase pathway. Science. 296:2002;1655-1657.
6. Cantley L.C., Neel B.G. New insights into tumor suppression. PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway Proc. Natl. Acad. Sci. USA. 96:1999;4240-4245.
7. Choe G., Horvath S., Cloughesy T.F., Crosby K., Seligson D., Palotie A., Inge L., Smith B.L., Sawyers C.L., Mischel P.S. Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res. 63:2003;2742-2746.
8. Chun K.H., Kosmeder J.W. 2nd, Sun S., Pezzuto J.M., Lotan R., Hong W.K., Lee H.Y. Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J. Natl. Cancer Inst. 95:2003;291-302.
9. Datta S.R., Brunet A., Greenberg M.E. Cellular survival. a play in three Akts Genes Dev. 13:1999;2905-2927.
10. Davies S.P., Reddy H., Caivano M., Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351:2000;95-105.
11. Di Cristofano A., Pesce B., Cordon-Cardo C., Pandolfi P.P. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19:1998;348-355.
12. Di Cristofano A., De Acetis M., Koff A., Cordon-Cardo C., Pandolfi P.P. Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27:2001;222-224.
13. Diehl J.A., Cheng M., Roussel M.F., Sherr C.J. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12:1998;3499-3511.
14. Djordjevic S., Driscoll P.C. Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases. Trends Biochem. Sci. 27:2002;426-432.
15. Dudkin L., Dilling M.B., Cheshire P.J., Harwood F.C., Hollingshead M., Arbuck S.G., Travis R., Sausville E.A., Houghton P.J. Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin. Cancer Res. 7:2001;1758-1764.
16. Eaton S.R., Cody W.L., Doherty A.M., Holland D.R., Panek R.L., Lu G.H., Dahring T.K., Rose D.R. Design of peptidomimetics that inhibit the association of phosphatidylinositol 3-kinase with platelet-derived growth factor-beta receptor and possess cellular activity. J. Med. Chem. 41:1998;4329-4342.
17. Fingar D.C., Salama S., Tsou C., Harlow E., Blenis J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16:2002;1472-1487.
18. Fulton D., Gratton J.P., McCabe T.J., Fontana J., Fujio Y., Walsh K., Franke T.F., Papapetropoulos A., Sessa W.C. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 399:1999;597-601.
19. Garami A., Zwartkruis F.J., Nobukuni T., Joaquin M., Roccio M., Stocker H., Kozma S.C., Hafen E., Bos J.L., Thomas G. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell. 11:2003;1457-1466.
20. Gomez M., Sampson J., Whittemore V. The Tuberous Sclerosis Complex. 1999;Oxford University Press, Oxford, England.
21. Hahn W.C., Weinberg R.A. Rules for making human tumor cells. N. Engl. J. Med. 347:2002;1593-1603.
22. Holland E.C., Celestino J., Dai C., Schaefer L., Sawaya R.E., Fuller G.N. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat. Genet. 25:2000;55-57.
23. Hu L., Hofmann J., Lu Y., Mills G.B., Jaffe R.B. Inhibition of phosphatidylinositol 3′-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res. 62:2002;1087-1092.
24. Kishimoto H., Hamada K., Saunders M., Backman S., Sasaki T., Nakano T., Mak T.W., Suzuki A. Physiological functions of pten in mouse tissues. Cell Struct. Funct. 28:2003;11-21.
25. Knuefermann C., Lu Y., Liu B., Jin W., Liang K., Wu L., Schmidt M., Mills G.B., Mendelsohn J., Fan Z. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 22:2003;3205-3212.
26. Komander, D., Kular, G.S., Bain, J., Elliott, M., Alessi, D.R., and Van Aalten, D.M. (2003). Structural basis for UCN-01 specificity and PDK1 inhibition. Biochem. J., in press.
27. Kozikowski A.P., Sun H., Brognard J., Dennis P.A. Novel PI analogues selectively block activation of the pro-survival serine/threonine kinase Akt. J. Am. Chem. Soc. 125:2003;1144-1145.
28. Kurose K., Gilley K., Matsumoto S., Watson P.H., Zhou X.P., Eng C. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat. Genet. 32:2002;355-357.
29. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R.et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1997;1943-1947.
30. Majumder P.K., Yeh J.J., George D.J., Febbo P.G., Kum J., Xue Q., Bikoff R., Ma H., Kantoff P.W., Golub T.R.et al. Prostate intraepithelial neoplasia induced by prostate restricted Akt activation. the MPAKT model Proc. Natl. Acad. Sci. USA. 100:2003;7841-7846.
31. Malik S.N., Brattain M., Ghosh P.M., Troyer D.A., Prihoda T., Bedolla R., Kreisberg J.I. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin. Cancer Res. 8:2002;1168-1171.
32. Malumbres M., Barbacid M. To cycle or not to cycle. a critical decision in cancer Nat. Rev. Cancer. 1:2001;222-231.
33. Manning B.D., Cantley L.C. United at last. the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling Biochem. Soc. Trans. 31:2003;573-578.
34. Mayo L.D., Donner D.B. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl. Acad. Sci. USA. 98:2001;11598-11603.
35. McMenamin M.E., Soung P., Perera S., Kaplan I., Loda M., Sellers W.R. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 59:1999;4291-4296.
36. Neshat M.S., Mellinghoff I.K., Tran C., Stiles B., Thomas G., Petersen R., Frost P., Gibbons J.J., Wu H., Sawyers C.L. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. USA. 98:2001;10314-10319.
37. Nolte R.T., Eck M.J., Schlessinger J., Shoelson S.E., Harrison S.C. Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat. Struct. Biol. 3:1996;364-374.
38. Onda H., Lueck A., Marks P.W., Warren H.B., Kwiatkowski D.J. Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J. Clin. Invest. 104:1999;687-695.
39. Ozes O.N., Mayo L.D., Gustin J.A., Pfeffer S.R., Pfeffer L.M., Donner D.B. NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature. 401:1999;82-85.
40. Pelengaris S., Khan M., Evan G. c-myc. more than just a matter of life and death Nat. Rev. Cancer. 2:2002;764-776.
41. Podsypanina K., Lee R.T., Politis C., Hennessy I., Crane A., Puc J., Neshat M., Wang H., Yang L., Gibbons J.et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc. Natl. Acad. Sci. USA. 98:2001;10320-10325.
42. Romashkova J.A., Makarov S.S. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 401:1999;86-90.
43. Ruggero D., Pandolfi P.P. Does the ribosome translate cancer? Nat. Rev. Cancer. 3:2003;179-192.
44. Saltiel A.R., Kahn C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414:2001;799-806.
45. Saunders R.N., Metcalfe M.S., Nicholson M.L. Rapamycin in transplantation. a review of the evidence Kidney Int. 59:2001;3-16.
46. Schmitt C.A. Senescence, apoptosis and therapy-cutting the lifelines of cancer. Nat. Rev. Cancer. 3:2003;286-295.
47. Sears R., Nuckolls F., Haura E., Taya Y., Tamai K., Nevins J.R. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 14:2000;2501-2514.
48. Shawver L.K., Slamon D., Ullrich A. Smart drugs. tyrosine kinase inhibitors in cancer therapy Cancer Cell. 1:2002;117-123.
49. Sherr C.J., Roberts J.M. CDK inhibitors. positive and negative regulators of G1-phase progression Genes Dev. 13:1999;1501-1512.
50. Skorski T., Bellacosa A., Nieborowska-Skorska M., Majewski M., Martinez R., Choi J.K., Trotta R., Wlodarski P., Perrotti D., Chan T.O.et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. EMBO J. 16:1997;6151-6161.
51. Steck P.A., Pershouse M.A., Jasser S.A., Yung W.K., Lin H., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T.et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15:1997;356-362.
52. Stiles B., Gilman V., Khanzenzon N., Lesche R., Li A., Qiao R., Liu X., Wu H. Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis. Mol. Cell. Biol. 22:2002;3842-3851.
53. Sugimoto Y., Whitman M., Cantley L.C., Erikson R.L. Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol. Proc. Natl. Acad. Sci. USA. 81:1984;2117-2121.
54. Thomas C.C., Deak M., Alessi D.R., van Aalten D.M. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Curr. Biol. 12:2002;1256-1262.
55. Trotman L.C., Pandolfi P.P. PTEN and p53. Who will get the upper hand? Cancer Cell. 3:2003;97-99.
56. Uhlmann E.J., Wong M., Baldwin R.L., Bajenaru M.L., Onda H., Kwiatkowski D.J., Yamada K., Gutmann D.H. Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann. Neurol. 52:2002;285-296.
57. Vivanco I., Sawyers C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer. 2:2002;489-501.
58. Welch H.C., Coadwell W.J., Stephens L.R., Hawkins P.T. Phosphoinositide 3-kinase-dependent activation of Rac. FEBS Lett. 546:2003;93-97.
59. Whitman M., Kaplan D.R., Schaffhausen B., Cantley L., Roberts T.M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 315:1985;239-242.
60. Whitman M., Downes C.P., Keeler M., Keller T., Cantley L. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature. 332:1988;644-646.
61. Xu W., Liu L.Z., Loizidou M., Ahmed M., Charles I.G. The role of nitric oxide in cancer. Cell Res. 12:2002;311-320.
62. Yang J., Cron P., Good V.M., Thompson V., Hemmings B.A., Barford D. Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP. Nat. Struct. Biol. 9:2002;940-944.
63. Yu Q., Geng Y., Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature. 411:2001;1017-1021.
64. Zhou B.P., Liao Y., Xia W., Zou Y., Spohn B., Hung M.C. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell Biol. 3:2001;973-982.