Targeting PI3K signalling in cancer: opportunities, challenges and limitations

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197

Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486

EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735

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

The phosphoinositide 3-kinase pathway

Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621

PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496

EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib

Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338

Isolation of rare circulating tumour cells in cancer patients by microchip technology

Nagrath, S., Sequist, L. V. D., Maheswaran, S., Bell, D. W., Irimia, D., Ulkus, L., Smith, M. R., Kwak, E. L., Digumarthy, S. R., Muzikansky, A., et al. (2007) · Nature · doi:10.1038/nature06385 · Cited by 3,595

High Frequency of Mutations of the PIK3CA Gene in Human Cancers

Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448

The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330

The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate

Maehama, T., & Dixon, J. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13375 · Cited by 3,104

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

Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers

Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-356 · Cited by 2,742

SH2 domains recognize specific phosphopeptide sequences

Songyang, Z. (1993) · Cell · doi:10.1016/0092-8674(93)90404-e · Cited by 2,620

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

Ras, PI(3)K and mTOR signalling controls tumour cell growth

Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019

Phosphatidylinositol-3-OH kinase direct target of Ras

Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911

Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)

Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,860

PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients

Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858

PI3K pathway alterations in cancer: variations on a theme

Yuan, T. L., & Cantley, L. C. (2008) · Oncogene · doi:10.1038/onc.2008.245 · Cited by 1,845

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

A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer

Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.030 · Cited by 1,627

Detection of Mutations in EGFR in Circulating Lung-Cancer Cells

Maheswaran, S., Sequist, L. V., Nagrath, S., Ulkus, L., Brannigan, B., Collura, C. V., Inserra, E., Diederichs, S., Iafrate, A. J., Bell, D. W., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0800668 · Cited by 1,617

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

Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors

Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442

SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity

Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S. Y., Huang, Q., Qin, J., & Su, B. (2006) · Cell · doi:10.1016/j.cell.2006.08.033 · Cited by 1,407

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

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer

Carpten, J. D., Faber, A. L., Horn, C. L., Donoho, G. P., Briggs, S., Robbins, C. M., Hostetter, G. H., Boguslawski, S. J., Moses, T. Y., Savage, S., et al. (2007) · Nature · doi:10.1038/nature05933 · Cited by 1,322

Targeting the PI3K-Akt pathway in human cancer

Luo, J., Manning, B. D., & Cantley, L. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00248-4 · Cited by 1,290

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

Cellular Function of Phosphoinositide 3-Kinases: Implications for Development, Immunity, Homeostasis, and Cancer

Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J. F., & Waterfield, M. D. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.615 · Cited by 1,230

Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation

Hirsch, E., Katanaev, V. L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F., & Wymann, M. P. (2000) · Science · doi:10.1126/science.287.5455.1049 · Cited by 1,209

Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity

Maira, S.-M., Stauffer, F., Brueggen, J., Furet, P., Schnell, C., Fritsch, C., Brachmann, S., Chène, P., De Pover, A., Schoemaker, K., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0017 · Cited by 1,134

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 1,111

Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer

Wang, S., Gao, J., Lei, Q., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G. V., Li, G., Roy-Burman, P., Nelson, P. S., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00215-0 · Cited by 1,109

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 1,080

Tenets of PTEN Tumor Suppression

Salmena, L., Carracedo, A., & Pandolfi, P. P. (2008) · Cell · doi:10.1016/j.cell.2008.04.013 · Cited by 1,050

Insulin Activation of Rheb, a Mediator of mTOR/S6K/4E-BP Signaling, Is Inhibited by TSC1 and 2

Garami, A., Zwartkruis, F. J. T., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., & Thomas, G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00220-x · Cited by 1,043

Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration

Sasaki, T., Irie-Sasaki, J., Jones, R. G., Oliveira-dos-Santos, A., Stanford, W. L., Bolon, B. N., Wakeham, A. C., Itié, A., Bouchard, D., Kozieradzki, I., et al. (2000) · Science · doi:10.1126/science.287.5455.1040 · Cited by 1,027

mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways

Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964

Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice

Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W. P., Meek, S. E., Salpekar, A., Waterfield, M. D., et al. (2002) · Science · doi:10.1126/science.1073560 · Cited by 948

Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems

Podsypanina, K., Ellenson, L. H., Nemes, A., Gu, J., Tamura, M., Yamada, K. M., Cordon‐Cardo, C., Cattoretti, G., Fisher, P. E., & Parsons, R. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1563 · Cited by 947

Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies

Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938

The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway

Sansal, I., & Sellers, W. R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.141 · Cited by 933

Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins

Zhang, Y., Gao, X., Saucedo, L. J., Ru, B., Edgar, B. A., & Pan, D. (2003) · Nature Cell Biology · doi:10.1038/ncb999 · Cited by 924

Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas

Bellacosa, A., de Feo, D., Godwin, A. K., Bell, D. W., Cheng, J. Q., Altomare, D. A., Wan, M., Dubeau, L., Scambia, G., Masciullo, V., et al. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910640412 · Cited by 837

Oncogenic PI3K deregulates transcription and translation

Bader, A. G., Kang, S., Zhao, L., & Vogt, P. K. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1753 · Cited by 807

Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.

Cheng, J. Q., Ruggeri, B., Klein, W. M., Sonoda, G., Altomare, D. A., Watson, D. K., & Testa, J. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3636 · Cited by 793

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

Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase

Nobukuni, T., Joaquin, M., Roccio, M., Dann, S. G., Kim, S. Y., Gulati, P., Byfield, M. P., Backer, J., Natt, F., Bos, J. L., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506925102 · Cited by 775

Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma.

Staal, S. P. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.14.5034 · Cited by 775

Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation

Whitman, M., Kaplan, D., Schaffhausen, B., Cantley, L., & Roberts, T. (1985) · Nature · doi:10.1038/315239a0 · Cited by 732

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

Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer

Engelman, J. A., & Janne, P. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2248 · Cited by 706

Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis

Jia, S., Liu, Z., Zhang, S., Liu, P., Zhang, L., Lee, S., Zhang, J., Signoretti, S., Loda, M. F., Roberts, T. M., et al. (2008) · Nature · doi:10.1038/nature07091 · Cited by 702

Pten Dose Dictates Cancer Progression in the Prostate

Trotman, L. C., Niki, M., Dotan, Z., Koutcher, J. A., Cristofano, A. D., Xiao, A., Khoo, A. S. B., Roy‐Burman, P., Greenberg, N. M., Dyke, T. V., et al. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000059 · Cited by 682

Class I PI3K in oncogenic cellular transformation

Zhao, L., & Vogt, P. K. (2008) · Oncogene · doi:10.1038/onc.2008.244 · Cited by 612

Crystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ

Pacold, M. E., Suire, S., Perišić, O., Lara‐González, S., Davis, C. T., Walker, E. H., Hawkins, P. T., Stephens, L., Eccleston, J. F., & Williams, R. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00196-3 · Cited by 611

Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action.

Yakes, F. M., Chinratanalab, W., Ritter, C. A., King, W., SEELIG, S. A., & Arteaga, C. L. (2002) · PubMed · Cited by 608

Binding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice

Gupta, S., Ramjaun, A. R., Haiko, P., Wang, Y., Warne, P. H., Nicke, B., Nye, E. L., Stamp, G., Alitalo, K. K., & Downward, J. (2007) · Cell · doi:10.1016/j.cell.2007.03.051 · Cited by 603

Mutations in a signalling pathway

Parsons, D. W., Wang, T., Samuels, Y., Bardelli, A., Cummins, J. M., Wood, L. D., Silliman, N., Ptak, J., Szabo, S., Willson, J. K. V., et al. (2005) · Nature · doi:10.1038/436792a · Cited by 599

PTEN: a tumour suppressor that functions as a phospholipid phosphatase

Maehama, T. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01519-6 · Cited by 591

Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition

Irie, H. Y., Pearline, R. V., Grueneberg, D. A., Hsia, M., Ravichandran, P., Kothari, N. H., Natesan, S., & Brugge, J. S. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505087 · Cited by 582

PTEN-deficient cancers depend on PIK3CB

Wee, S., Wiederschain, D., Maira, S., Loo, A. T., Miller, C., deBeaumont, R. S., Stegmeier, F., Yao, Y.-M. M., & Lengauer, C. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0802655105 · Cited by 565

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

A Family with Severe Insulin Resistance and Diabetes Due to a Mutation in AKT2

George, S., Rochford, J. J., Wolfrum, C., Gray, S. L., Schinner, S., Wilson, J. C., Soos, M. A., Murgatroyd, P. R., Williams, R. M., Acerini, C. L., et al. (2004) · Science · doi:10.1126/science.1096706 · Cited by 562

Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo.

Moulder, S. L., Yakes, F. M., Muthuswamy, S. K., Bianco, R., Simpson, J. F., & Arteaga, C. L. (2001) · PubMed · Cited by 548

hVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase

Byfield, M. P., Murray, J. T., & Backer, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507201200 · Cited by 540

Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration

Graupera, M., Guillermet-Guibert, J., Foukas, L., Phng, L.-K., Cain, R., Salpekar, A., Pearce, W., Meek, S., Millán, J., Cutillas, P., et al. (2008) · Nature · doi:10.1038/nature06892 · Cited by 532

Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins

Guix, M., Faber, A. C., Wang, S. E., Olivares, M. G., Song, Y., Qu, S., Rinehart, C., Seidel, B., Yee, D., Arteaga, C. L., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34588 · Cited by 525

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 522

ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines

Engelman, J. A., Janne, P. A., Mermel, C. H., Pearlberg, J., Mukohara, T., Fleet, C., Cichowski, K. M., Johnson, B. E., & Cantley, L. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409773102 · Cited by 500

Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235

Eichhorn, P. J. A., Gili, M., Scaltriti, M., Serra, V., Guzman, M., Nijkamp, W., Beijersbergen, R. L., Valero, V., Seoane, J., Bernards, R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1740 · Cited by 499

Drug discovery approaches targeting the PI3K/Akt pathway in cancer

Garcı́a-Echeverrı́a, C., & Sellers, W. R. (2008) · Oncogene · doi:10.1038/onc.2008.246 · Cited by 485

mTOR and cancer therapy

Easton, J. B., & Houghton, P. J. (2006) · Oncogene · doi:10.1038/sj.onc.1209886 · Cited by 468

PI3Kγ Modulates the Cardiac Response to Chronic Pressure Overload by Distinct Kinase-Dependent and -Independent Effects

Patrucco, E., Notte, A., Barberis, L., Selvetella, G., Maffei, A., Brancaccio, M., Marengo, S., Russo, G., Azzolino, O., Rybalkin, S. D., et al. (2004) · Cell · doi:10.1016/j.cell.2004.07.017 · Cited by 465

Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer

Engelman, J. A., Mukohara, T., Zejnullahu, K., Lifshits, E., Borras, A. M., Gale, C.-M., Naumov, G. N., Yeap, B. Y., Jarrell, E., Sun, J., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28656 · Cited by 457

The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors.

Philp, A., Campbell, I., Leet, C. S. F., Vincan, E., Rockman, S., Whitehead, R. H., Thomas, R. J., & Phillips, W. A. (2001) · PubMed · Cited by 455

Signalling by PI3K isoforms: insights from gene-targeted mice

Vanhaesebroeck, B., Ali, K., Bilancio, A., Geering, B., & Foukas, L. C. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.02.008 · Cited by 450

Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors

Bianco, R., Shin, I., Ritter, C. A., Yakes, F. M., Basso, A., Rosen, N. X., Tsurutani, J., Dennis, P. A., Mills, G. B., & Arteaga, C. L. (2003) · Oncogene · doi:10.1038/sj.onc.1206388 · Cited by 449

Helical domain and kinase domain mutations in p110α of phosphatidylinositol 3-kinase induce gain of function by different mechanisms

Zhao, L., & Vogt, P. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712169105 · Cited by 449

A Crucial Role for the p110δ Subunit of Phosphatidylinositol 3-Kinase in B Cell Development and Activation

Clayton, E., Bardi, G., Bell, S. E., Chantry, D., Downes, C. P., Gray, A., Humphries, L. A., Rawlings, D. J., Reynolds, H., Vigorito, E., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020805 · Cited by 446

Proliferative Defect and Embryonic Lethality in Mice Homozygous for a Deletion in the p110α Subunit of Phosphoinositide 3-Kinase

Bi, L., Okabe, I., Bernard, D. J., Wynshaw-Boris, A. J., & Nussbaum, R. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10963 · Cited by 444

PIK3CA as an oncogene in cervical cancer

Ma, Y.-Y., Wei, S., Lin, Y., Lung, J.-C., Chang, T.-C., Whang‐Peng, J., Liu, J. M., Yang, D.-M., Yang, W. K., & Shen, C. (2000) · Oncogene · doi:10.1038/sj.onc.1203597 · Cited by 432

Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells

Hideshima, T., Catley, L. P., Yasui, H., Ishitsuka, K., Raje, N. S., Mitsiades, C. S., Podar, K., Munshi, N. C., Chauhan, D., Richardson, P. G. G., et al. (2006) · Blood · doi:10.1182/blood-2005-08-3434 · Cited by 423

The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells

She, Q., Solit, D. B., Ye, Q., O'Reilly, K. E., Lobo, J. M., & Rosen, N. X. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.09.006 · Cited by 416

Mechanism of Two Classes of Cancer Mutations in the Phosphoinositide 3-Kinase Catalytic Subunit

Miled, N., Yan, Y., Hon, W., Perišić, O., Zvelebil, M., Inbar, Y., Schneidman‐Duhovny, D., Wolfson, H. J., Backer, J., & Williams, R. L. (2007) · Science · doi:10.1126/science.1135394 · Cited by 410

Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation.

Kondapaka, S. B., Singh, S. S., Dasmahapatra, G. P., Sausville, E. A., & Roy, K. K. (2003) · PubMed · Cited by 402

Essential, Nonredundant Role for the Phosphoinositide 3-Kinase p110δ in Signaling by the B-Cell Receptor Complex

Jou, S., Carpino, N., Takahashi, Y., Piekorz, R. P., Chao, J.-R., Carpino, N., Wang, D., & Ihle, J. N. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8580-8591.2002 · Cited by 357

Pharmacologic Characterization of a Potent Inhibitor of Class I Phosphatidylinositide 3-Kinases

Raynaud, F. I., Eccles, S. A., Clarke, P. A., Hayes, A., Nutley, B. P., Alix, S., Henley, A. T., Di-Stefano, F., Ahmad, Z., Guillard, S., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4615 · Cited by 354

PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer

Ogino, S., Nosho, K., Kirkner, G. J., Shima, K., Irahara, N., Kure, S., Chan, A. T., Engelman, J. A., Kraft, P. L., Cantley, L. C., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.6544 · Cited by 331

Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase

Bi, L., Okabe, I., Bernard, D. J., & Nussbaum, R. L. (2002) · Mammalian Genome · doi:10.1007/bf02684023 · Cited by 317

Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling

Ihle, N. T., Williams, R. R., Chow, S., Chew, W. M., Berggren, M. I., Paine-Murrieta, G. D., Minion, D. J., Halter, R. J., Wipf, P., Abraham, R. T., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.763.3.7 · Cited by 317

Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

Rhodes, N., Heerding, D. A., Duckett, D. R., Eberwein, D. J., Knick, V. B., Lansing, T. J., McConnell, R. T., Gilmer, T. M., Zhang, S., Robell, K. A., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5783 · Cited by 299

Acquired resistance to tyrosine kinase inhibitors during cancer therapy

Engelman, J. A., & Settleman, J. E. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.01.004 · Cited by 292

Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKCλ/ζ

Taniguchi, C. M., Kondo, T., Sajan, M. P., Luo, J., Bronson, R. T., Asano, T., Farese, R. V., Cantley, L. C., & Kahn, C. R. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.005 · Cited by 288

Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer—A Study from the IMPACT Trialists

Dowsett, M., Ebbs, S. R., Dixon, J. M., Skene, A. I., Griffith, C. D. M., Boeddinghaus, I., Salter, J., DETRE, S. I., Hills, M., Ashley, S., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.559 · Cited by 287

A Vascular Targeted Pan Phosphoinositide 3-Kinase Inhibitor Prodrug, SF1126, with Antitumor and Antiangiogenic Activity

Garlich, J. R., De, P. K. R., Dey, N., Su, J. D., Peng, X., Miller, A., Murali, R., Lu, Y., Mills, G. B., Kundra, V., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-0669 · Cited by 280

Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance

Ihle, N. T., Lemos, R., Wipf, P., Yacoub, A., Mitchell, C., Siwak, D. R., Mills, G. B., Dent, P., Kirkpatrick, D. L., & Powis, G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6656 · Cited by 275

Phosphoinositide 3‐kinases in cell migration

Cain, R. J., & Ridley, A. J. (2008) · Biology of the Cell · doi:10.1042/bc20080079 · Cited by 268

A novel AKT3 mutation in melanoma tumours and cell lines

Davies, M. A., Stemke‐Hale, K., Tellez, C. S., Calderone, T. L., Deng, W., Prieto, V. G., Lazar, A. J., Gershenwald, J. E., & Mills, G. B. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604637 · Cited by 268

A New Mutational aktivation in the PI3K Pathway

Brugge, J. S., Hung, M., & Mills, G. B. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.07.014 · Cited by 264

Heterodimeric Phosphoinositide 3-Kinase Consisting of p85 and p110β Is Synergistically Activated by the βγ Subunits of G Proteins and Phosphotyrosyl Peptide

Kurosu, H., Maehama, T., Okada, T., Yamamoto, T., Hoshino, S.-I., Fukui, Y., Ui, M., Hazeki, O., & Katada, T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.39.24252 · Cited by 260

The Mammalian Target of Rapamycin Signaling Pathway: Twists and Turns in the Road to Cancer Therapy

Abraham, R. T., & Gibbons, J. J. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2798 · Cited by 244

Essential role for the p110 isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia

Sujobert, P. (2005) · Blood · doi:10.1182/blood-2004-08-3225 · Cited by 243

Akt1 Ablation Inhibits, whereas Akt2 Ablation Accelerates, the Development of Mammary Adenocarcinomas in Mouse Mammary Tumor Virus (MMTV)-ErbB2/Neu and MMTV-Polyoma Middle T Transgenic Mice

Maroulakou, I. G., Oemler, W., Naber, S. P., & Tsichlis, P. N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3782 · Cited by 242

Transient Potent BCR-ABL Inhibition Is Sufficient to Commit Chronic Myeloid Leukemia Cells Irreversibly to Apoptosis

Shah, N. P., Kasap, C., Weier, C. A., Balbas, M., Nicoll, J. M., Bleickardt, E. W., Nicaise, C., & Sawyers, C. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.001 · Cited by 231

Signaling network of the Btk family kinases

Qiu, Y., & Kung, H.-J. (2000) · Oncogene · doi:10.1038/sj.onc.1203958 · Cited by 225

Non-parametric quantification of protein lysate arrays

Hu, J., He, X., Baggerly, K., Coombes, K. R., Hennessy, B. T., & Mills, G. B. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm283 · Cited by 224

Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway.

Massion, P. P., Kuo, W.-L., Stokoe, D., Olshen, A. B., TRESELER, P. A., Chin, K., Chen, C., Polikoff, D., Jain, A. N., Pinkel, D., et al. (2002) · PubMed · Cited by 222

Perifosine: Update on a novel Akt inhibitor

Gills, J. J., & Dennis, P. A. (2009) · Current Oncology Reports · doi:10.1007/s11912-009-0016-4 · Cited by 221

United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling

Manning, B. D., & Cantley, L. C. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310573 · Cited by 211

Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non–Small Cell Lung Cancer Cell Line

Ogino, A., Kitao, H., Hirano, S., Uchida, A., Ishiai, M., Kozuki, T., Takigawa, N., Takata, M., Kiura, K., & Tanimoto, M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0681 · Cited by 194

A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN -Mutant Glioma

Fan, Q.-W., Cheng, C. K., Nicolaides, T. P., Hackett, C. S., Knight, Z. A., Shokat, K. M., & Weiss, W. A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2154 · Cited by 192

Activating E17K mutation in the gene encoding the protein kinase AKT in a subset of squamous cell carcinoma of the lung

Malanga, D., Scrima, M., Marco, C. D., Fabiani, F., Rosa, N. D., Gisi, S. D., Malara, N., Savino, R., Rocco, G., Chiappetta, G., et al. (2008) · Cell Cycle · doi:10.4161/cc.7.5.5485 · Cited by 190

Regulation of the p85/p110α Phosphatidylinositol 3′-Kinase

Yu, J., Wjasow, C., & Backer, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30199 · Cited by 187

Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma

Byun, D., Cho, K., Ryu, B., Lee, M., Park, J., Chae, K. S., Kim, H. J., & Chi, S. (2003) · International Journal of Cancer · doi:10.1002/ijc.10962 · Cited by 184

Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin

Rini, B. I. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4719 · Cited by 183

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 178

Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis

Rychahou, P. G., Kang, J., Gulhati, P., Doan, H. Q., Chen, L. A., Xiao, S., Chung, D. H., & Evers, B. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810715105 · Cited by 177

Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition

Han, E. K.-H., Leverson, J. D., McGonigal, T. P., Shah, O. J., Woods, K. W., Hunter, T. R., Giranda, V. L., & Luo, Y. (2007) · Oncogene · doi:10.1038/sj.onc.1210343 · Cited by 169

Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase

Heerding, D. A., Rhodes, N., Leber, J. D., Clark, T. J., Keenan, R. M., LaFrance, L. V., Li, M., Safonov, I. G., Takata, D. T., Venslavsky, J. W., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8004527 · Cited by 168

High-Resolution Melting Analysis for Rapid Detection ofKRAS, BRAF,andPIK3CAGene Mutations in Colorectal Cancer

Simi, L., Pratesi, N., Vignoli, M., Sestini, R., Cianchi, F., Valanzano, R., Nobili, S., Mini, E., Pazzagli, M., & Orlando, C. (2008) · American Journal of Clinical Pathology · doi:10.1309/lwdy1axhxuulnvhq · Cited by 166

A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16

Billottet, C., Grandage, V., Gale, R. E., Quattropani, A., Rommel, C., Vanhaesebroeck, B., & Khwaja, A. (2006) · Oncogene · doi:10.1038/sj.onc.1209670 · Cited by 155

Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma

Woenckhaus, J., Steger, K., Werner, E., Fenic, I., Gamerdinger, U., Dreyer, T., & Stahl, U. (2002) · The Journal of Pathology · doi:10.1002/path.1207 · Cited by 152

Mechanism ofcyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: Analysis of allele-specific expression

Hosokawa, Y., & Arnold, A. (1998) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199805)22:1 · Cited by 149

Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta.

Sawyer, C., Sturge, J., Bennett, D. C., O’Hare, M. J., Allen, W. E., Bain, J., Jones, G. E., & Vanhaesebroeck, B. (2003) · PubMed · Cited by 147

BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

Velho, S., Moutinho, C., Cirnes, L., Albuquerque, C. M., Hamelin, R., Schmitt, F. C., Carneiro, F., Oliveíra, C., & Seruca, R. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-255 · Cited by 145

Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemias

Kim, M. S., Jeong, E. G., Yoo, N. J., & Lee, S. H. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604212 · Cited by 140

A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isotype-selective inhibition

Torbett, N., Luna-Moran, A., Knight, Z. A., Houk, A., Moasser, M., Weiss, W., Shokat, K., & Stokoe, D. (2008) · Biochemical Journal · doi:10.1042/bj20080639 · Cited by 138

Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia.

Miller, C. T., Moy, J. R., Lin, L., Schipper, M. J., Normolle, D. P., Brenner, D. E., Iannettoni, M. D., Orringer, M. B., & Beer, D. G. (2003) · PubMed · Cited by 135

The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures

Howes, A. L., Chiang, G. G., Lang, E. S., Ho, C., Powis, G., Vuori, K., & Abraham, R. T. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0698 · Cited by 135

mTOR inhibitors in the treatment of cancer

Fasolo, A., & Sessa, C. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.11.1717 · Cited by 132

A Function for Phosphatidylinositol 3-Kinase β (p85α-p110β) in Fibroblasts during Mitogenesis: Requirement for Insulin- and Lysophosphatidic Acid-Mediated Signal Transduction

Roche, S., Downward, J., Raynal, P., & Courtneidge, S. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.7119 · Cited by 128

Pharmacodynamic Markers of Perifosine Efficacy

Hennessy, B. T., Lu, Y., Poradosu, E., Yu, Q., Yu, S., Hall, H. S., Carey, M. S., Ravoori, M. K., Gonzalez-Angulo, A. M., Birch, R., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0760 · Cited by 127

Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment.

Stein, R. C. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080237 · Cited by 127

Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma

Dunlap, J. B., Le, C., Shukla, A., Patterson, J., Presnell, A., Heinrich, M. C., Corless, C. L., & Troxell, M. L. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0406-1 · Cited by 122

Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt

Yamasaki, F., Johansen, M. J., Zhang, D., Krishnamurthy, S., Felix, E. A., Bartholomeusz, C., Aguilar, R. J., Kurisu, K., Mills, G. B., Hortobágyi, G. N., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3020 · Cited by 118

Effects of oncogenic p110α subunit mutations on the lipid kinase activity of phosphoinositide 3-kinase

Carson, J. D., Aller, G. V., Lehr, R. V., Sinnamon, R. H., Kirkpatrick, R. B., Auger, K. R., Dhanak, D., Copeland, R. A., Gontarek, R. R., Tummino, P. J., et al. (2007) · Biochemical Journal · doi:10.1042/bj20070681 · Cited by 116

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

Guix, M., Granja, N. D. M., Meszoely, I. M., Adkins, T. B., Wieman, B. M., Frierson, K. E., Sanchez, V., Sanders, M. E., Grau, A. M., Mayer, I. A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.5939 · Cited by 111

Class 1A PI3K regulates vessel integrity during development and tumorigenesis

Yuan, T. L., Choi, H. S., Matsui, A., Benes, C. H., Lifshits, E., Luo, J., Frangioni, J. V., & Cantley, L. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804123105 · Cited by 99

mTOR Pathway and mTOR Inhibitors as Agents for Cancer Therapy

Baldo, P., Cecco, S., Giacomin, E., Lazzarini, R., Rós, B. D. T., & Marastoni, S. (2008) · Current Cancer Drug Targets · doi:10.2174/156800908786733513 · Cited by 97

Discovery of Drug-Resistant and Drug-Sensitizing Mutations in the Oncogenic PI3K Isoform p110α

Zunder, E. R., Knight, Z. A., Houseman, B. T., Apsel, B., & Shokat, K. M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.014 · Cited by 96

Mechanism of Constitutive Phosphoinositide 3-Kinase Activation by Oncogenic Mutants of the p85 Regulatory Subunit

Shekar, S. C., Wu, H., Fu, Z., Yip, S.-C., Nagajyothi, Cahill, S. M., Girvin, M. E., & Backer, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506005200 · Cited by 85

Phosphoinositide 3-OH kinase p85α and p110β are essential for androgen receptor transactivation and tumor progression in prostate cancers

Zhu, Q., Youn, H., Tang, J., Tawfik, O. W., Dennis, K. L., Terranova, P. F., Du, J., Raynal, P., Thrasher, J. B., & Li, B. (2008) · Oncogene · doi:10.1038/onc.2008.91 · Cited by 80

Phosphatidylinositol 3-Kinase Mediates Bronchioalveolar Stem Cell Expansion in Mouse Models of Oncogenic K-ras-Induced Lung Cancer

Yang, Y., Iwanaga, K., Raso, M. G., Wislez, M., Hanna, A. E., Wieder, E., Molldrem, J. J., Wistuba, I. I., Powis, G., DeMayo, F. J., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002220 · Cited by 79

Targeting the PI3K p110α Isoform Inhibits Medulloblastoma Proliferation, Chemoresistance, and Migration

Stücklin, A. G., Fattet, S., Fischer, B. E., Shalaby, T., Jackson, S. P., Schoenwaelder, S. M., Grotzer, M. A., Delattre, O., & Arcaro, A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0385 · Cited by 77

Targeting the Phosphoinositide 3-Kinase Isoform p110δ Impairs Growth and Survival in Neuroblastoma Cells

Boller, D., Schramm, A. R., Doepfner, K. T., Shalaby, T., von Bueren, A. O., Eggert, A., Grotzer, M. A., & Arcaro, A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0737 · Cited by 74

Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation and triggers apoptosis in acute promyelocytic leukemia without affecting atra-induced differentiation.

Billottet, C., Banerjee, L., Vanhaesebroeck, B., & Khwaja, A. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2608 · Cited by 61

Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometry.

Cutillas, P., Khwaja, A., Graupera, M., Pearce, W., Gharbi, S., Waterfield, M., & Vanhaesebroeck, B. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0602101103 · Cited by 41

The PPARγ agonist pioglitazone prevents the hyperglycemia caused by phosphoinositide-3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Ihle, N., Lemos, R., Schwartz, D., Oh, J., Halter, R., Wipf, P., Kirkpatrick, L., & Powis, G. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0714 · Cited by 30

Mutation analysis of the human homologue ofdrosophila patched and the xeroderma pigmentosum complementation group A genes in squamous cell carcinomas of the skin

Eklund, L. K., Lindström, E., Undén, A. B., Lundh-Rozell, B., Ståhle‐Bäckdahl, M., Zaphiropoulos, P. G., Toftgård, R., & Söderkvist, P. (1998) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199802)21:2 · Cited by 23

Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies

Flinn, I. W., Byrd, J. C., Furman, R. R., Brown, J. R., Lin, T. S., Bello, C., Giese, N. A., & Yu, A. S. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.3543 · Cited by 18

Cell Signaling by Receptor Tyrosine Kinases

Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929

The molecular biology of head and neck cancer

Leemans, C. R., Braakhuis, B. J. M., & Brakenhoff, R. H. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2982 · Cited by 2,640

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138

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He, Y., Sun, M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 2,045

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Hidalgo, M. M., Amant, F. C., Biankin, A. V., Budínská, E., Byrne, A. T., Caldas, C., Clarke, R. B., de Jong, S., Jonkers, J., Mælandsmo, G. M., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0001 · Cited by 1,797

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Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785

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Dancey, J. E. (2004) · Annals of Oncology · doi:10.1093/annonc/mdh932 · Cited by 54

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Alam, M., Ali, S., & Hassan, M. I. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91287-7.00006-5 · Cited by 6

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