Cited by 2,445PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerCancer, Lipids, and Metabolism

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Targeting PI3K signalling in cancer: opportunities, challenges and limitations

Engelman, Jeffrey A.·2009·Nature Reviews Cancer

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Abstract

There are ample genetic and laboratory studies that suggest the PI3K-Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of drugs targeting PI3K-Akt signalling for the treatment of cancer is discussed. I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development.

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She, Q., Chandarlapaty, S., Ye, Q., Lobo, J. M., Haskell, K., Leander, K. R., Defeo-Jones, D., Huber, H. E., & Rosen, N. X. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003065 · Cited by 313
Retracted
Retracted: Frequent genetic and biochemical alterations of the PI 3‐K/AKT/PTEN pathway in head and neck squamous cell carcinoma
Garcia-Pedrero, J. M., García‐Carracedo, D., Pinto, C. M., Zapatero, A. H., Rodrigo, J. P., Nieto, C. S., & González, M. V. (2004) · International Journal of Cancer · doi:10.1002/ijc.20711 · Cited by 235
Retracted
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
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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
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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
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Bi, L., Okabe, I., Bernard, D. J. & Nussbaum, R. L. Early embryonic lethality in mice deficient in the p110b catalytic subunit of PI3-kinase. Mamm. Genome 13, 169–172 (2002).

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Noren Hooten, N., Abdelmohsen, K., Gorospe, M., Ejiogu, N., Zonderman, A. B., & Evans, M. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010724 · Cited by 357
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Phosphoinositide signalling in cancer: beyond PI3K and PTEN
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Fabbro, D., Cowan‐Jacob, S. W., & Möbitz, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13096 · Cited by 365
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Elkabets, M., Vora, S., Juric, D., Morse, N., Mino-Kenudson, M., Muranen, T., Tao, J., Campos, A. B., Rodon, J., Ibrahim, Y. H., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005747 · Cited by 332
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Jankú, F., Tsimberidou, A. M., Garrido‐Laguna, I., Wang, X., Luthra, R., Hong, D. S., Naing, A., Falchook, G. S., Moroney, J. W., Piha-Paul, S. A., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0994 · Cited by 333
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Elkabets, M., Pazarentzos, E., Juric, D., Sheng, Q., Pelossof, R. A., Brook, S., Benzaken, A. O., Rodon, J., Morse, N., Yan, J. J., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.010 · Cited by 325
Therapeutic Strategies for Targeting Ras Proteins
Gysin, S., Salt, M. B., Young, A. E., & McCormick, F. (2011) · Genes & Cancer · doi:10.1177/1947601911412376 · Cited by 329
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Zoi, V., Galani, V., Lianos, G. D., Voulgaris, S., Kyritsis, A. P., & Alexiou, G. Α. (2021) · Biomedicines · doi:10.3390/biomedicines9091086 · Cited by 353
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Gil, E. M. C. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.03.004 · Cited by 325
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Bohdanowicz, M., & Grinstein, S. (2013) · Physiological Reviews · doi:10.1152/physrev.00002.2012 · Cited by 326
Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end?
Tanaka, S., Louis, D. N., Curry, W. T., Batchelor, T. T., & Dietrich, J. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.204 · Cited by 317
AKT Inhibition in Solid Tumors With AKT1 Mutations
Hyman, D. M., Smyth, L. M., Donoghue, M. T. A., Westin, S. N., Bedard, P. L., Dean, E. J., Bando, H., El-Khoueiry, A. B., Fidalgo, J. A. P., Mita, A. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.73.0143 · Cited by 313
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Hao, Y., Samuels, Y., Li, Q., Krokowski, D., Guan, B.-J., Wang, C., Jin, Z., Dong, B., Cao, B., Feng, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms11971 · Cited by 290
Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia
Park, S., Chapuis, N., Tamburini, J., Bardet, V., Cornillet‐Lefèbvre, P., Willems, L., Green, A. S., Mayeux, P., Lacombe, C., & Bouscary, D. (2009) · Haematologica · doi:10.3324/haematol.2009.013797 · Cited by 315
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Jankú, F., Wheler, J. J., Naing, A., Falchook, G. S., Hong, D. S., Stepanek, V. M. T., Fu, S., Piha-Paul, S. A., Lee, J. J., Luthra, R., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1726 · Cited by 300
Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics
Krakstad, C., & Chekenya, M. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-135 · Cited by 310
Receptor Tyrosine Kinase-Targeted Cancer Therapy
Yamaoka, T., Kusumoto, S., Ando, K., Ohba, M., & Ohmori, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113491 · Cited by 297
Bone Microenvironment and Osteosarcoma Metastasis
Yang, C., Tian, Y. E., Zhao, F., Chen, Z., Su, P., Li, Y., & Qian, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21196985 · Cited by 298

Authors: Engelman, J. A.
Affiliations: Massachusetts General Hospital (US)
Corresponding author: Engelman, Jeffrey A.
ORCID: Engelman, Jeffrey A.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2009-08
Volume: 9
Issue: 8
Pages: 550-562
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2664
OpenAlex: W1977267072
Cited by: 2,445
References: 160
Citations by year: 2026: 60 · 2025: 71 · 2024: 75 · 2023: 102 · 2022: 90 · 2021: 125 · 2020: 146 · 2019: 127 · 2018: 163 · 2017: 172 · 2016: 159 · 2015: 210 · 2014: 211 · 2013: 221 · 2012: 184
FWCI: 13.17
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: PI3K/Akt signaling, PI3K inhibitors, AKT inhibitors, cancer therapy, targeted therapy, drug development, tumor cell survival, treatment resistance
MeSH terms: Antineoplastic Agents, Humans, Neoplasms, Protein Kinases, Signal Transduction, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases

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Targeting PI3K signalling in cancer: opportunities, challenges and limitations

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