The DOI matches its Crossref record; 159 of the 160 references it cites were found in a registry or an index.
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
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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Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“AKT, through a series of complex signal transduction cascades, leads to the activation of the mTOR1 complex (Engelman, 2009).”
From Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab (2011) · cites this paper as Engelman, 2009
In the citing paper
“These include mutation and/or amplification of the genes encoding the PI3K catalytic subunits p110α (PIK3CA) and p110β (PIK3CB), the PI3K regulatory subunit p85α (PIK3R1), the PI3K effectors AKT1, AKT2, and PDK1, and loss of the lipid phosphatases PTEN and INPP4B [reviewed in (Engelman, 2009)].”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Engelman, 2009
In the citing paper
“Somatic alterations in the PI3K/AKT pathway are the most frequent in breast cancer, occurring in approximately 30% of HER2+ tumors.”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Engelman, 2009
Citations
Cites
2 retracted
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
RetractedGarcia-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
RetractedUnderstanding 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
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
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
Self-citation
Flagged first, then by citations
1 of the 160 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 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).
Cited by
Sorted by citations
Items 1,001–1,005 of 1,005
Zhang, X., Birtwistle, M., & Gallo, J. (2014) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1038/psp.2013.65 · Cited by 33
Does PtdIns(4,5)P 2 concentrate so it can multi-task?
Hammond, G. R. V. (2016) · Biochemical Society Transactions · doi:10.1042/bst20150211 · Cited by 28
Estrogen signaling in the proliferative endometrium: implications in endometriosis
Silva, R. D. C. P. D. C. E., Moura, K. K. V. D. O., Ribeiro Júnior, C. L., & Guillo, L. A. (2016) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.62.01.72 · Cited by 21
Promising efficacy of novel BTK inhibitor AC0010 in mantle cell lymphoma
Yan, X., Zhou, Y., Huang, S., Li, X., Yu, M., Huang, J., Wang, J., Ma, Z., Jin, J., Pan, J., et al. (2018) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-017-2570-8 · Cited by 12
Non-pharmacological management of gestational diabetes: The role of myo-inositol
Guardo, F. D., Currò, J. M., Valenti, G., Rossetti, P., Di Gregorio, L. M., Conway, F., Chiofalo, B., Garzon, S., Bruni, S., & Rizzo, G. (2020) · Journal of Complementary and Integrative Medicine · doi:10.1515/jcim-2019-0111 · Cited by 14
Metadata
- Authors
- Engelman, J. A.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Engelman, Jeffrey A.
- ORCID
- Engelman, Jeffrey A.
- Venue
- Nature Reviews Cancer
- Published
- 2009-08
- Volume
- 9
- Issue
- 8
- Pages
- 550-562
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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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