PI3K pathway alterations in cancer: Variations on a theme

Oncogene

Volumn 27, Issue 41, 2008, Pages 5497-5510

  Yuan, T L ^a   Cantley, L C ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

HER2; PI3K; PTEN; Tumorigenesis

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 2 (2 DIFLUOROMETHYLBENZIMIDAZOL 1 YL) 4,6 DIMORPHOLINO 1,3,5 TRIAZINE; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 MORPHOLINO 8 PHENYLCHROMONE; 5 (4 BROMO 2 CHLOROANILINO) 4 FLUORO 1 METHYL 1H BENZIMIDAZOLE 6 CARBOHYDROXAMIC ACID 2 HYDROXYETHYL ESTER; BGT 226; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; GEFITINIB; IMATINIB; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; P110 ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PIK 90; PIK 93; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PROTEIN KINASE B; PROTEIN P110; RAPAMYCIN; RDEA 119; SF 1126; TEMSIROLIMUS; TRASTUZUMAB; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; WORTMANNIN; XL 147; XL 518; XL 765;

ANTINEOPLASTIC ACTIVITY; BINDING SITE; BREAST CANCER; CANCER INHIBITION; CANCER RADIOTHERAPY; CARCINOGENESIS; CARCINOGENICITY; CLINICAL TRIAL; GENE MUTATION; GLIOBLASTOMA; GLUCOSE METABOLISM; HUMAN; IC 50; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; METASTASIS; MONOTHERAPY; NONHUMAN; ONCOGENE NEU; ONCOGENE RAS; PRIORITY JOURNAL; REVIEW; SOLID TUMOR;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ENZYME INHIBITORS; GENES, ERBB-2; GENES, RAS; HUMANS; MODELS, BIOLOGICAL; MUTATION; NEOPLASMS; NUCLEAR PROTEINS; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 51849111556     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2008.245     Document Type: Review

References (85)

1. Abubaker J, Bavi P, Al-Harbi S, Ibrahim M, Siraj AK, Al-Sanea N et al. (2008). Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population. Oncogene 27: 3539-3545.
2. Arteaga CL. (2006). EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans. Cancer Cell 9: 421-423.
3. Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S et al. (2004). The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 3: 772-775.
4. Barault L, Veyrie N, Jooste V, Lecorre D, Chapusot C, Ferraz JM et al. (2008). Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer 122: 2255-2259.
5. Barnes KR, Blois J, Smith A, Yuan H, Reynolds F, Weissleder R et al. (2008). Fate of a bioactive fluorescent wortmannin derivative in cells. Bioconjug Chem 19: 130-137.
6. Bauer S, Duensing A, Demetri GD, Fletcher JA. (2007). KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene 26: 7560-7568.
7. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K et al. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12: 395-402.
8. Bissell MJ, Radisky D. (2001). Putting tumours in context. Nat Rev Cancer 1: 46-54.
9. Buck E, Eyzaguirre A, Brown E, Petti F, McCormack S, Haley JD et al. (2006). Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non-small-cell lung, pancreatic, colon, and breast tumors. Mol Cancer Ther 5: 2676-2684.
10. Cantley LC. (2002). The phosphoinositide 3-kinase pathway. Science 296: 1655-1657.
11. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM et al. (2007). A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448: 439-444.
12. Chen JS, Zhou LJ, Entin-Meer M, Yang X, Donker M, Knight ZA et al. (2008). Characterization of structurally distinct, isoform-selective phosphoinositide 3′-kinase inhibitors in combination with radiation in the treatment of glioblastoma. Mol Cancer Ther 7: 841-850.
13. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M et al. (2005). Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436: 725-730.
14. Crabbe T, Welham MJ, Ward SG. (2007). The PI3K inhibitor arsenal: choose your weapon!. Trends Biochem Sci 32: 450-456.
15. Downward J. (2003). Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3: 11-22.
16. Engelman JA. (2007). The role of phosphoinositide 3-kinase pathway inhibitors in the treatment of lung cancer. Clin Cancer Res 13: s4637-s4640.
17. Engelman JA, Janne PA, Mermel C, Pearlberg J, Mukohara T, Fleet C et al. (2005). ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci USA 102: 3788-3793.
18. Engelman JA, Luo J, Cantley LC. (2006). The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7: 606-619.
19. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO et al. (2007). MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316: 1039-1043.
20. Fan QW, Cheng CK, Nicolaides TP, Hackett CS, Knight ZA, Shokat KM et al. (2007). A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res 67: 7960-7965.
21. Fan QW, Knight ZA, Goldenberg DD, Yu W, Mostov KE, Stokoe D et al. (2006). A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 9: 341-349.
22. Folkman J. (2007). Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6: 273-286.
23. Fujita T, Doihara H, Kawasaki K, Takabatake D, Takahashi H, Washio K et al. (2006). PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer. Br J Cancer 94: 247-252.
24. Furuyama T, Kitayama K, Shimoda Y, Ogawa M, Sone K, Yoshida-Araki K et al. (2004). Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice. J Biol Chem 279: 34741-34749.
25. Garlich JR, De P, Dey N, Su JD, Peng X, Miller A et al. (2008). A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res 68: 206-215.
26. Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A et al. (2008). Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature 453: 662-666.
27. Gupta GP, Massague J. (2006). Cancer metastasis: building a framework. Cell 127: 679-695.
28. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B et al. (2007). Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 129: 957-968.
29. Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J et al. (2005). The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev 19: 2054-2065.
30. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H et al. (2004). The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166: 213-223.
31. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N et al. (2003). PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299: 708-710.
32. Hendriks BS, Opresko LK, Wiley HS, Lauffenburger D. (2003). Coregulation of epidermal growth factor receptor/human epidermal growth factor receptor 2 (HER2) levels and locations: quantitative analysis of HER2 overexpression effects. Cancer Res 63: 1130-1137.
33. Hirata A, Hosoi F, Miyagawa M, Ueda S, Naito S, Fujii T et al. (2005). HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells. Cancer Res 65: 4253-4260.
34. Hirsch E, Ciraolo E, Ghigo A, Costa C. (2008). Taming the PI3K team to hold inflammation and cancer at bay. Pharmacol Ther 118: 192-205.
35. Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L et al. (2000). Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287: 1049-1053.
36. Hofer E, Schweighofer B. (2007). Signal transduction induced in endothelial cells by growth factor receptors involved in angiogenesis. Thromb Haemost 97: 355-363.
37. Hollestelle A, Elstrodt F, Nagel JH, Kallemeijn WW, Schutte M. (2007). Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines. Mol Cancer Res 5: 195-201.
38. Howes AL, Chiang GG, Lang ES, Ho CB, Powis G, Vuori K et al. (2007). The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures. Mol Cancer Ther 6: 2505-2514.
39. Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW et al. (2007). The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 318: 1744-1748.
40. Ikeda T, Yoshinaga K, Suzuki A, Sakurada A, Ohmori H, Horii A. (2000). Anticorresponding mutations of the KRAS and PTEN genes in human endometrial cancer. Oncol Rep 7: 567-570.
41. Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV et al. (2005). Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 65: 10992-11000.
42. Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS et al. (2008). PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res 68: 1953-1961.
43. Kang S, Seo SS, Chang HJ, Yoo CW, Park SY, Dong SM. (2008). Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma. Int J Gynecol Cancer; e-pub ahead of print.
44. Kato S, Iida S, Higuchi T, Ishikawa T, Takagi Y, Yasuno M et al. (2007). PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer 121: 1771-1778.
45. Kim JS, Lee C, Bonifant CL, Ressom H, Waldman T. (2007). Activation of p53-dependent growth suppression in human cells by mutations in PTEN or PIK3CA. Mol Cell Biol 27: 662-677.
46. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O et al. (2006). A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 125: 733-747.
47. Kolsch V, Charest PG, Firtel RA. (2008). The regulation of cell motility and chemotaxis by phospholipid signaling. J Cell Sci 121: 551-559.
48. Kong D, Yamori T. (2007). ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. Cancer Sci 98: 1638-1642.
49. Koyasu S. (2003). The role of PI3K in immune cells. Nat Immunol 4: 313-319.
50. Li D, Shimamura T, Ji H, Chen L, Haringsma HJ, McNamara K et al. (2007). Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 12: 81-93.
51. Lim KH, Counter CM. (2005). Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance. Cancer Cell 8: 381-392.
52. Martin-Belmonte F, Mostov K. (2008). Regulation of cell polarity during epithelial morphogenesis. Curr Opin Cell Biol 20: 227-234.
53. Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ et al. (2005). Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353: 2012-2024.
54. Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y et al. (2007). Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 317: 239-242.
55. Moasser MM. (2007). The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26: 6469-6487.
56. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA et al. (2004). PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6: 117-127.
57. Narita Y, Nagane M, Mishima K, Huang HJ, Furnari FB, Cavenee WK. (2002). Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas. Cancer Res 62: 6764-6769.
58. Oda K, Stokoe D, Taketani Y, McCormick F. (2005). High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res 65: 10669-10673.
59. Ollikainen M, Gylling A, Puputti M, Nupponen NN, Abdel-Rahman WM, Butzow R et al. (2007). Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma. Int J Cancer 121: 915-920.
60. Perez-Tenorio G, Alkhori L, Olsson B, Waltersson MA, Nordenskjold B, Rutqvist LE et al. (2007). PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 13: 3577-3584.
61. Ramjaun AR, Downward J. (2007). Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis. Cell Cycle 6: 2902-2905.
62. Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ et al. (1994). Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370: 527-532.
63. Rommel C, Camps M, Ji H. (2007). PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat Rev Immunol 7: 191-201.
64. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X et al. (2005). PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65: 2554-2559.
65. Salmena L, Carracedo A, Pandolfi PP. (2008). Tenets of PTEN tumor suppression. Cell 133: 403-414.
66. Samuels Y, Diaz Jr LA, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I et al. (2005). Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7: 561-573.
67. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S et al. (2004). High frequency of mutations of the PIK3CA gene in human cancers. Science 304: 554.
68. Sarkisian CJ, Keister BA, Stairs DB, Boxer RB, Moody SE, Chodosh LA. (2007). Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nat Cell Biol 9: 493-505.
69. Sauter G, Maeda T, Waldman FM, Davis RL, Feuerstein BG. (1996). Patterns of epidermal growth factor receptor amplification in malignant gliomas. Am J Pathol 148: 1047-1053.
70. Soltoff SP, Carraway III KL, Prigent SA, Gullick WG, Cantley LC. (1994). ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol 14: 3550-3558.
71. Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J et al. (2004). Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431: 525-526.
72. Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R et al. (2007). Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318: 287-290.
73. Suire S, Hawkins P, Stephens L. (2002). Activation of phosphoinositide 3-kinase gamma by Ras. Curr Biol 12: 1068-1075.
74. Sun JF, Phung T, Shiojima I, Felske T, Upalakalin JN, Feng D et al. (2005). Microvascular patterning is controlled by fine-tuning the Akt signal. Proc Natl Acad Sci USA 102: 128-133.
75. Tokunaga E, Oki E, Kimura Y, Yamanaka T, Egashira A, Nishida K et al. (2007). Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma. Breast Cancer Res Treat 101: 249-257.
76. Tornillo L, Terracciano LM. (2006). An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 59: 557-563.
77. Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz Jr S et al. (2005). The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 41: 1649-1654.
78. Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP et al. (2000). Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 6: 909-919.
79. Walker EH, Perisic O, Ried C, Stephens L, Williams RL. (1999). Structural insights into phosphoinositide 3-kinase catalysis and signalling. Nature 402: 313-320.
80. Wang MY, Lu KV, Zhu S, Dia EQ, Vivanco I, Shackleford GM et al. (2006). Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells. Cancer Res 66: 7864-7869.
81. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al. (2004). BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64: 7099-7109.
82. Wymann MP, Bulgarelli-Leva G, Zvelebil MJ, Pirola L, Vanhaesebroeck B, Waterfield MD et al. (1996). Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol 16: 1722-1733.
83. Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H et al. (2006). Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst 98: 545-556.
84. Yuan H, Barnes KR, Weissleder R, Cantley L, Josephson L. (2007). Covalent reactions of wortmannin under physiological conditions. Chem Biol 14: 321-328.
85. Zhao L, Vogt PK. (2008). Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci USA 105: 2652-2657.