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

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

Engelman, Jeffrey A.·2009·Nature Reviews Cancer

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1038/nrc2664

Cites

159 of 159 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

2 retracted

RETRACTED: Breast Tumor Cells with PI3K Mutation or HER2 Amplification Are Selectively Addicted to Akt Signaling
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
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
Self-citation

Flagged first, then by citations

Show all 160 references

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).

Sorted by citations

Items 101–200 of 1,005

Tyrosine kinase gene rearrangements in epithelial malignancies
Shaw, A. T., Hsu, P. P., Awad, M. M., & Engelman, J. A. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3612 · Cited by 295
Self-citation
The sphingosine 1-phosphate receptor S1P2 maintains the homeostasis of germinal center B cells and promotes niche confinement
Green, J. A., Suzuki, K., Cho, B. K., Willison, L. D., Palmer, D., Allen, C. D. C., Schmidt, T. H., Xu, Y., Proia, R. L., Coughlin, S. R., et al. (2011) · Nature Immunology · doi:10.1038/ni.2047 · Cited by 282
Cartilage tumours and bone development: molecular pathology and possible therapeutic targets
Bovée, J. V. M. G., Hogendoorn, P. C. W., Wunder, J. S., & Alman, B. A. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2869 · Cited by 282
The molecular pathology of cancer
Harris, T., & McCormick, F. P. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.41 · Cited by 286
The epidermal growth factor network: role in oocyte growth, maturation and developmental competence
Richani, D., & Gilchrist, R. B. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmx029 · Cited by 281
Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab
Brand, T. M., Iida, M., & Wheeler, D. L. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.9.15050 · Cited by 287
Mechanism-based cancer therapy: resistance to therapy, therapy for resistance
Ramos, P. M., & Bentires‐Alj, M. (2014) · Oncogene · doi:10.1038/onc.2014.314 · Cited by 287
O-GlcNAcylation: A New Cancer Hallmark?
Fardini, Y., Dehennaut, V., Lefebvre, T., & Issad, T. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00099 · Cited by 275
Emerging roles of aerobic glycolysis in breast cancer
Wu, Z., Wu, J., Zhao, Q., Fu, S., & Jin, J. (2019) · Clinical & Translational Oncology · doi:10.1007/s12094-019-02187-8 · Cited by 264
Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics
Akinleye, A., Avvaru, P., Furqan, M., Song, Y., & Liu, D. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-88 · Cited by 260
Energy Balance, Host-Related Factors, and Cancer Progression
Hursting, S. D., & Berger, N. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.27.9935 · Cited by 257
The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients
Martelli, A. M., Evangelisti, C., Chiarini, F., & McCubrey, J. A. (2010) · Oncotarget · doi:10.18632/oncotarget.114 · Cited by 251
Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer
Lien, E. C., Lyssiotis, C. A., Juvekar, A., Hu, H., Asara, J. M., Cantley, L. C., & Toker, A. (2016) · Nature Cell Biology · doi:10.1038/ncb3341 · Cited by 249
Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives
Saunders, N. A., Simpson, F., Thompson, E. W., Hill, M. M. C., Endo‐Munoz, L., Leggatt, G. R., Minchin, R. F., & Guminski, A. D. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201101131 · Cited by 252
Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling
Qian, C., Lai, C.-J., Bao, R., Wang, D.-G., Wang, J., Xu, G.-X., Atoyan, R., Qu, H., Yin, L., Samson, M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0055 · Cited by 248
Genistein: Its role in metabolic diseases and cancer
Mukund, V., Mukund, D., Sharma, V., Mannarapu, M., & Alam, A. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.09.004 · Cited by 251
The Extending Network of FOXO Transcriptional Target Genes
van der Vos, K. E., & Coffer, P. J. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3419 · Cited by 249
Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis
Brown, G. T., & Murray, G. I. (2015) · The Journal of Pathology · doi:10.1002/path.4586 · Cited by 242
JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer
Britschgi, A., Andraos, R., Brinkhaus, H., Klebba, I., Romanet, V., Müller, U., Murakami, M., Radimerski, T., & Bentires‐Alj, M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.10.023 · Cited by 247
First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas
Patnaik, A., Appleman, L., Tolcher, A., Papadopoulos, K., Beeram, M., Rasco, D., Weiss, G., Sachdev, J., Chadha, M., Fulk, M., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw282 · Cited by 218
Signal Transduction Pathways in Breast Cancer: The Important Role of PI3K/Akt/mTOR
Ortega, M. A., Fraile‐Μartinez, O., Asúnsolo, Á., Buján, J., García‐Honduvilla, N., & Coca, S. (2020) · Journal of Oncology · doi:10.1155/2020/9258396 · Cited by 253
Adiponectin Regulates Bone Mass via Opposite Central and Peripheral Mechanisms through FoxO1
Kajimura, D., Lee, H. W., Riley, K. J., Arteaga‐Solis, E., Ferron, M., Zhou, B., Clarke, C. J., Hannun, Y. A., DePinho, R. A., Guo, X.-D. E., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.009 · Cited by 244
Mesoporous Silica Nanoparticles Facilitate Delivery of siRNA to Shutdown Signaling Pathways in Mammalian Cells
Hom, C., Lu, J., Liong, M., Luo, H.-Z., Li, Z., Zink, J. I., & Tamanoi, F. (2010) · Small · doi:10.1002/smll.200901966 · Cited by 240
PTEN and PI3K/AKT in Non-Small-Cell Lung Cancer
Pérez-Ramírez, C., Cañadas‐Garre, M., Molina‐Vila, M. Á., Faus-Dáder, M. J., & Calleja‐Hernández, M. Á. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.122 · Cited by 246
Assessing PIK3CA and PTEN in Early-Phase Trials with PI3K/AKT/mTOR Inhibitors
Jankú, F., Hong, D. S., Fu, S., Piha-Paul, S. A., Naing, A., Falchook, G. S., Tsimberidou, A. M., Stepanek, V. M. T., Moulder, S., Lee, J. J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.035 · Cited by 237
Targeting Cell Signaling and Apoptotic Pathways by Dietary Agents: Role in the Prevention and Treatment of Cancer
Shanmugam, M. K., Kannaiyan, R., & Sethi, G. (2011) · Nutrition and Cancer · doi:10.1080/01635581.2011.523502 · Cited by 236
The PTEN/PI3K/AKT Pathway in vivo, Cancer Mouse Models
Carnero, A., & Paramio, J. M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00252 · Cited by 241
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 236
The Pathophysiology of Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor-β in Normal and Malignant Mammary Epithelial Cells
Taylor, M. A., Parvani, J. G., & Schiemann, W. P. (2010) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-010-9181-1 · Cited by 235
PIK3R1 (p85α) Is Somatically Mutated at High Frequency in Primary Endometrial Cancer
Urick, M. E., Rudd, M. L., Godwin, A. K., Sgroi, D. C., Merino, M. J., & Bell, D. W. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0549 · Cited by 236
TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation
Ou, Y.-H., Torres, M. J., Ram, R. R., Formstecher, É., Roland, C. L., Cheng, T., Brekken, R. A., Wurz, R. P., Tasker, A. S., Polverino, T., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.01.019 · Cited by 224
Designing nanomedicine for immuno-oncology
Jiang, W., Roemeling, C. A. V., Chen, Y., Qie, Y., Liu, X., Chen, J., & Kim, B. Y. S. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0029 · Cited by 230
Mitochondria in cancer
Grasso, D., Zampieri, L. X., Capelôa, T., de Velde, J. A. V., & Sonveaux, P. (2020) · Cell Stress · doi:10.15698/cst2020.06.221 · Cited by 239
The crucial role of multiomic approach in cancer research and clinically relevant outcomes
Lu, M., & Zhan, X. (2018) · The EPMA Journal · doi:10.1007/s13167-018-0128-8 · Cited by 235
Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review)
Shi, X., Wang, J., Yu, L., Cong, C., Tan, D., & Zhou, X. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10121 · Cited by 226
PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kα Inhibition
Castel, P., Ellis, H., Bago, R., Toska, E., Razavi, P., Carmona, F. J., Kannan, S., Verma, C. S., Dickler, M. N., Chandarlapaty, S., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.06.004 · Cited by 230
Discovery of a Potent, Selective, and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor (GDC-0980) for the Treatment of Cancer
Sutherlin, D. P., Bao, L., Berry, M., Castanedo, G. M., Chuckowree, I., Dotson, J., Folks, A., Friedman, L. S., Goldsmith, R. A., Gunzner, J. L., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2009327 · Cited by 224
A Unique Spectrum of Somatic PIK3CA (p110α) Mutations Within Primary Endometrial Carcinomas
Rudd, M. L., Price, J. C., Fogoros, S. K., Godwin, A. K., Sgroi, D. C., Merino, M. J., & Bell, D. W. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0540 · Cited by 222
Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition
Katsuno, Y., Meyer, D. S., Zhang, Z., Shokat, K. M., Akhurst, R. J., Miyazono, K., & Derynck, R. (2019) · Science Signaling · doi:10.1126/scisignal.aau8544 · Cited by 219
Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial
Soulières, D., Faivre, S. J., Mesı́a, R., Remenár, É., Li, S.-H., Karpenko, A., Dechaphunkul, A., Ochsenreither, S., Kiss, L. A., Lin, J., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30064-5 · Cited by 219
The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges
Cheaib, B., Auguste, A., & Leary, A. F. (2015) · 癌症：英文版 · doi:10.5732/cjc.014.10289 · Cited by 226
Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non–Small-Cell Lung Cancer
Papadimitrakopoulou, V. A. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31825493eb · Cited by 220
Somatic PIK3CA mutations as a driver of sporadic venous malformations
Castel, P., Carmona, F. J., Grego‐Bessa, J., Berger, M. F., Viale, A. J., Anderson, K. V., Bagué, S., Scaltriti, M., Antonescu, C. R., Baselga, E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf1164 · Cited by 213
Tumour Angiogenesis and Angiogenic Inhibitors: A Review
Yadav, L. (2015) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2015/12016.6135 · Cited by 216
Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer
Nunnery, S. E., & Mayer, I. A. (2020) · Drugs · doi:10.1007/s40265-020-01394-w · Cited by 225
Targeting the PI3K-AKT-mTOR signaling network in cancer
Khan, K. H., Yap, T. A., Li, Y., & Cunningham, D. (2013) · 癌症：英文版 · doi:10.5732/cjc.013.10057 · Cited by 217
Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein
Abbastabar, M., Kheyrollah, M., Azizian, K., Bagherlou, N., Tehrani, S. S., Maniati, M., & Karimian, A. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.07.008 · Cited by 219
Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer
Lien, E. C., Lyssiotis, C. A., & Cantley, L. C. (2016) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-319-42118-6_3 · Cited by 217
PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1
Ebi, H., Costa, C., Faber, A. C., Nishtala, M. V., Kotani, H., Juric, D., Pelle, P. D., Song, Y., Yano, S., Mino-Kenudson, M. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314124110 · Cited by 214
Self-citation
Integrating Network Pharmacology and Pharmacological Evaluation for Deciphering the Action Mechanism of Herbal Formula Zuojin Pill in Suppressing Hepatocellular Carcinoma
Guo, W., Huang, J., Wang, N., Tan, H., Cheung, F., Chen, F., & Feng, Y. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01185 · Cited by 211
Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy
Yu, X., Long, Y. C., & Shen, H. (2015) · Autophagy · doi:10.1080/15548627.2015.1043076 · Cited by 212
PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers
Jankú, F., Lee, J. J., Tsimberidou, A. M., Hong, D. S., Naing, A., Falchook, G. S., Fu, S., Luthra, R., Garrido‐Laguna, I., & Kurzrock, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022769 · Cited by 207
Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research
Hursting, S. D., Smith, S. M., Lashinger, L. M., Harvey, A. E., & Perkins, S. N. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp280 · Cited by 209
Measurement of PIP3 Levels Reveals an Unexpected Role for p110β in Early Adaptive Responses to p110α-Specific Inhibitors in Luminal Breast Cancer
Costa, C., Ebi, H., Martini, M., Beausoleil, S. A., Faber, A., Jakubik, C. T., Huang, A., Wang, Y., Nishtala, M., Hall, B., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.11.007 · Cited by 192
Self-citation
Accelerated wound healing by mTOR activation in genetically defined mouse models
Squarize, C. H., Castilho, R. M., Bugge, T. H., & Gutkind, J. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010643 · Cited by 203
Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies
Hanker, A. B., Pfefferle, A. D., Balko, J. M., Kuba, M. G., Young, C. D., Sánchez, V., Sutton, C. R., Cheng, H., Perou, C. M., Zhao, J. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303204110 · Cited by 203
Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium
Smith, S. M., van Besien, K., Karrison, T. G., Dancey, J. E., McLaughlin, P. J., Younes, A., Smith, S. E., Stiff, P. J., Lester, E. P., Modi, S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.2813 · Cited by 203
Myc proteins as therapeutic targets
Gustafson, W. C., & Weiss, W. A. (2010) · Oncogene · doi:10.1038/onc.2009.512 · Cited by 204
Coexistence of PIK3CA and Other Oncogene Mutations in Lung Adenocarcinoma–Rationale for Comprehensive Mutation Profiling
Chaft, J. E., Arcila, M. E., Paik, P. K., Lau, C., Riely, G. J., Pietanza, M. C., Zakowski, M. F., Rusch, V. W., Sima, C. S., Ladanyi, M., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0692 · Cited by 202
PI3K and mTOR Signaling Pathways in Cancer: New Data on Targeted Therapies
Willems, L., Tamburini, J., Chapuis, N., Lacombe, C., Mayeux, P., & Bouscary, D. (2012) · Current Oncology Reports · doi:10.1007/s11912-012-0227-y · Cited by 208
PIK3CA Mutations May Be Discordant between Primary and Corresponding Metastatic Disease in Breast Cancer
Jensen, J. D., Lænkholm, A., Knoop, A. S., Ewertz, M., Bandaru, R., Liu, W., Hackl, W., Barrett, J. C., & Gardner, H. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1133 · Cited by 201
Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary
Jamieson, S., & Fuller, P. J. (2012) · Endocrine Reviews · doi:10.1210/er.2011-0014 · Cited by 205
Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin
Bhagwat, S. V., Gokhale, P. C., Crew, A. P. A., Cooke, A., Yao, Y., Mantis, C., Kahler, J., Workman, J. E., Bittner, M., Dudkin, L., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-1099 · Cited by 203
Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways
Pandurangan, A. K. (2013) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2013.14.4.2201 · Cited by 198
Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression
Li, Y., Zeng, C., Hu, J., Pan, Y., Shan, Y., Liu, B., & Li, J. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0632-2 · Cited by 198
OBESITY AS A RISK FACTOR FOR CANCER
Tzenios, N. (2023) · EPRA International Journal of Multidisciplinary Research (IJMR) · doi:10.36713/epra12423 · Cited by 197
Mechanism of resistance to endocrine therapy in breast cancer: the important role of PI3K/Akt/mTOR in estrogen receptor-positive, HER2-negative breast cancer
Araki, K., & Miyoshi, Y. (2017) · Breast Cancer · doi:10.1007/s12282-017-0812-x · Cited by 201
Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling
Tato, I., Bartrons, R., Ventura, F., & Rosa, J. L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.166991 · Cited by 201
PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment
Leiphrakpam, P., & Are, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063178 · Cited by 193
Oncogenes in Cell Survival and Cell DeathPreprint
Shortt, J., & Johnstone, R. W. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009829 · Cited by 200
PGC1α Promotes Tumor Growth by Inducing Gene Expression Programs Supporting Lipogenesis
Bhalla, K., Hwang, B. J., Dewi, R. E., Ou, L., Twaddel, W., Fang, H., Vafai, S. B., Vazquez, F., Puigserver, P., Boros, L. G., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1011 · Cited by 195
PI3K mutations in breast cancer: prognostic and therapeutic implications
Mukohara, T. (2015) · Breast Cancer Targets and Therapy · doi:10.2147/bctt.s60696 · Cited by 189
Genetic Changes in Squamous Cell Lung Cancer: A Review
Heist, R. S., Sequist, L. V. D., & Engelman, J. A. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31824cc334 · Cited by 197
Self-citation
Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer
Cima, I., Schiess, R., Wild, P. J., Kaelin, M., Schüffler, P. J., Lange, V., Picotti, P., Ossola, R., Templeton, A. J., Schubert, O. T., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013699108 · Cited by 190
PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs
Weigelt, B., Warne, P. H., & Downward, J. (2011) · Oncogene · doi:10.1038/onc.2011.42 · Cited by 191
Copper Promotes Tumorigenesis by Activating the PDK1‐AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner
Guo, J., Cheng, J., Zheng, N., Zhang, X., Dai, X., Zhang, L., Hu, C.-J., Wu, X., Jiang, Q., Wu, D., et al. (2021) · Advanced Science · doi:10.1002/advs.202004303 · Cited by 198
Clinical update on cancer: molecular oncology of head and neck cancer
Suh, Y., Amelio, I., Urbano, T. G., & Tavassoli, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2013.548 · Cited by 195
Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors
Rodon, J. A., Braña, I., Siu, L. L., Jonge, M. J. D., Homji, N. F., Mills, D., di Tomaso, E., Sarr, C., Trandafir, L., Massacesi, C., et al. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0082-9 · Cited by 190
Re-evaluating the role of FOXOs in cancer
Hornsveld, M., Dansen, T. B., Derksen, P. W. B., & Burgering, B. M. T. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.017 · Cited by 184
Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer
Sanchez, C. G., Ma, C. X., Crowder, R. J., Guintoli, T., Phommaly, C., Gao, F., Li, L., & Ellis, M. J. (2011) · Breast Cancer Research · doi:10.1186/bcr2833 · Cited by 184
Potential Applications of NRF2 Inhibitors in Cancer Therapy
Panieri, E., & Saso, L. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8592348 · Cited by 189
FOXM1 (Forkhead box M1) in Tumorigenesis
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407190-2.00016-2 · Cited by 190
Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors
Molife, L. R., Li, Y., Vitfell-Rasmussen, J., Zernhelt, A. M., Sullivan, D. M., Cassier, P. A., Chen, E. X., Biondo, A., Tetteh, E., Siu, L. L., et al. (2014) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-7-1 · Cited by 183
Requirement of the mTOR Kinase for the Regulation of Maf1 Phosphorylation and Control of RNA Polymerase III-dependent Transcription in Cancer Cells
Shor, B., Wu, J., Shakey, Q., Toral‐Barza, L., Shi, C., Follettie, M. T., & Yu, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.071639 · Cited by 195
Medical therapies for meningiomas
Wen, P. Y., Lee, E. Q., Drappatz, J., Beroukhim, R., & Norden, A. D. (2010) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0349-8 · Cited by 180
A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2– advanced breast cancer (BELLE-4)
Martín, M., Chan, A., Dirix, L. Y., O’Shaughnessy, J., Hegg, R., Manikhas, A., Shtivelband, M. I., Криворотько, П. В., López, N. B., Campone, M., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw562 · Cited by 180
Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling
Fu, H., Wang, C., Yang, D., Wei, Z., Xu, J., Hu, Z., Zhang, Y. X., Wang, W., Yan, R., & Cai, Q. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26190 · Cited by 180
Dependence on the MUC1-C Oncoprotein in Non–Small Cell Lung Cancer Cells
Raina, D. B., Kosugi, M., Ahmad, R., Panchamoorthy, G., Rajabi, H. N., Alam, M., Shimamura, T., Shapiro, G. I., Supko, J. G., Kharbanda, S. M., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-1050 · Cited by 185
KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment
Zeitouni, D., Pylayeva‐Gupta, Y., Der, C. J., & Bryant, K. L. (2016) · Cancers · doi:10.3390/cancers8040045 · Cited by 191
Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor
Aller, G. S. V., Carson, J. D., Tang, W. D., Peng, H., Zhao, L., Copeland, R. A., Tummino, P. J., & Luo, L. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.02.010 · Cited by 178
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors)
Reinwald, M., Silva, J. T., Mueller, N. J., Fortün, J., Garzoni, C., de Fijter, J. W., Fernández‐Ruiz, M., Grossi, P., & Aguado, J. M. (2018) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2018.02.009 · Cited by 178
Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis
Jeng, H., Taylor, L. J., & Bar‐Sagi, D. (2012) · Nature Communications · doi:10.1038/ncomms2173 · Cited by 176
Antitumor Efficacy of PKI-587, a Highly Potent Dual PI3K/mTOR Kinase Inhibitor
Mallon, R. G., Feldberg, L. R., Lucas, J., Chaudhary, I., Dehnhardt, C. M., Santos, E. D., Chen, Z., dos Santos, O., Ayral‐Kaloustian, S., Venkatesan, A. M., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1694 · Cited by 181
Identification of a Role for the PI3K/AKT/mTOR Signaling Pathway in Innate Immune Cells
Xie, S., Chen, M., Yan, B., He, X., Chen, X.-W., & Li, D.-W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094496 · Cited by 165
Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Mayer, I. A., Abramson, V. G., Isakoff, S. J., Forero, A., Balko, J. M., Kuba, M. G., Sanders, M. E., Yap, J. T., den Abbeele, A. D. V., Li, Y., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.0518 · Cited by 179
What We Have Learned About Pancreatic Cancer From Mouse Models
Pérez-Mancera, P. A., Guerra, C. E., Barbacid, M., & Tuveson, D. A. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.03.002 · Cited by 178
Polyphenols as small molecular inhibitors of signaling cascades in carcinogenesis
Kang, N. J., Shin, S. H., Lee, H. J., & Lee, K. W. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.02.004 · Cited by 174
Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP
Mirzaa, G., Rivière, J., & Dobyns, W. B. (2013) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31361 · Cited by 173
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas
Samartzis, E. P., Noske, A., Dedes, K. J., Fink, D. A., & Imesch, P. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140918824 · Cited by 180
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong, D. S., Bowles, D. W., Falchook, G. S., Messersmith, W. A., George, G. C., O’Bryant, C. L., Vo, A. C. H., Klucher, K. M., Herbst, R. S., Eckhardt, S., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0714 · Cited by 171

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Targeting PI3K signalling in cancer: opportunities, challenges and limitations

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks