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A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
Open accessAbstract
Summary Molecular alterations involving PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets. In addition to mutation, structural variations and partial copy losses involving PTEN and STK11 showed evidence for having functional relevance. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.
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“In particular, the occurrence of E545K at exon 9 and H1047R at exon 20 is prevalent in cancers, and these mutations can constitutively activate PI3K signaling32,33.”
From Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization (2025) · cites this paper as [32]
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“In particular, the occurrence of E545K at exon 9 and H1047R at exon 20 is prevalent in cancers, and these mutations can constitutively activate PI3K signaling32,33.”
From Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization (2025) · cites this paper as [32]
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455 · cited 1×
“Mutation Assessor calls predicting the functional impact (medium to high) of somatic mutation (Reva et al., 2011) were obtained from cBioPortal (Cerami et al., 2012).”
MethodNishimura, R., Osako, T., Nishiyama, Y., Tashima, R., Nakano, M., Fujisue, M., Toyozumi, Y., & Arima, N. (2013) · Oncology · doi:10.1159/000353099 · Cited by 13,239
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692 · cited 2×
“‘‘Tumor type corrected’’ survival p values denote significant correlation in model incorporating both the molecular feature and cancer type. p Values <0.05 correspond to an estimated false discovery rate (Storey and Tibshirani, 2003) of <10%.”
BackgroundInfluentialmTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · cited 2×
“Furthermore, AKT phosphorylates TSC2 at multiple sites, to inhibit the GTPase-activating protein function of the TSC protein complex (consisting of TSC1, TSC2, and TBC1D7) toward Rheb, a RAS family member (Dibble and Manning, 2013; Laplante and Sabatini, 2012).”
BackgroundAKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115 · cited 1×
“AKT directly and indirectly phosphorylates many downstream proteins, including the GSKs, p27KIP1, FoxO transcription factors, MDM2, and BAD, to enhance cell survival and growth (Manning and Cantley, 2007).”
BackgroundMutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419 · cited 3×
“A number of genes in the pathway were found significantly mutated or copy altered in pan-cancer analyses (Chang et al., 2016; Kandoth et al., 2013; Lawrence et al., 2014; Zack et al., 2013), including PIK3CA 4 Cancer Cell 31, 1–13, June 12, 2017 (14% mutated across all cancers; 6% amplified), PTEN…”
BackgroundComprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network (2013) · Nature · doi:10.1038/nature12222 · Cited by 3,485
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Hölzen, L., Parigiani, M. A., & Reinheckel, T. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140423 · Cited by 15
Update on the role of copanlisib in hematologic malignancies
Le, T. A. T., David, J., & Bryan, L. J. (2021) · Therapeutic Advances in Hematology · doi:10.1177/20406207211006027 · Cited by 15
Shen, S., Ji-wen, W., Dexiang, Z., Bohao, Z., Wang, Y., Liu, H., Ni, X., Suo, T., & Liu, H. (2019) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2019.1654361 · Cited by 15
“vated PI3K transferred PIP2 to PIP3 on cytomembrane, the second signaling [10,11].”
BackgroundLiang, L., Yang, B. Y., Wu, Y., & Sun, L. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10605 · Cited by 15
Regulation of transcriptome plasticity by mTOR signaling pathway
Yong, J., Kim, H., Lee, E., & Jung, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01508-y · Cited by 17
Self-citationMetabolic protein kinase signalling in neuroblastoma
Smiles, W. J., Catalano, L., Stefan, V. E., Weber, D. D., & Kofler, B. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101771 · Cited by 16
“These include activation mutations in PIK3CA (encoding the PI3K catalytic subunit), loss-of-function mutations in or deletions to PTEN, RTK amplification, and amplification and gain-of-function mutations in genes encoding Akt (which exists as three isoforms) [54,65].”
BackgroundPLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate
Chessa, T. A. M., Jung, P., Anwar, A., Suire, S., Anderson, K. E., Barneda, D., Kielkowska, A., Sadiq, B. A., Lai, I. W., Felisbino, S. L., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.07.015 · Cited by 15
Proteomic signatures of clear cell renal cell carcinoma
Creighton, C. J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0233-5 · Cited by 14
Self-citationMiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer
Cui, X., Lv, Z., Ding, H.-X., Xing, C., & Yuan, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.531244 · Cited by 14
Sunoqrot, S., Aliyeh, S., Abusulieh, S., & Sabbah, D. A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091977 · Cited by 14
Shen, M., Chen, S., Han, X., Hao, Y., Wang, J., Luo, L., Chen, T., Wang, B., Zou, L., Zhang, T., et al. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03729-y · Cited by 13
Sen, A., Khan, S. A., Rossetti, S., Broege, A., MacNeil, I. A., DeLaForest, A., Molden, J. S., Davis, L., Iversrud, C., Seibel, M. I., et al. (2024) · Molecular Oncology · doi:10.1002/1878-0261.13703 · Cited by 16
“Further review of the literature also reported the PAM pathway involvement in driving cancer regardless of PAM pathway gene mutations [45].”
Nguyen, L. T. T., Thompson, E., Bhimani, N., Duong, M. C., Nguyen, H. G., Bullock, M., Gild, M. L., & Glover, A. R. (2025) · Cancers · doi:10.3390/cancers17060939 · Cited by 17
Zhou, W., Ouyang, J., Li, J., Liu, F., An, T., Cheng, L.-J., Kuo, Z. C., Zhang, C., & He, Y. (2021) · Journal of Cancer · doi:10.7150/jca.55719 · Cited by 13
“In multiple previously published studies, PI3K/AKT signaling pathway has been reported to play carcinogenic roles in various cancers and to be related with tumor growth and prognosis of patients [22].”
BackgroundLiu, Q., Xiao, Q., Sun, Z., Wang, B., Wang, L., Wang, N., Wang, K., Song, C., & Yang, Q. (2021) · eLife · doi:10.7554/elife.69454 · Cited by 13
“Furthermore, the gene-specific correlation between mRNA and protein levels allows quantitative analyses of individual gene expression as an indicator for the corresponding protein (Peng et al., 2015; Uhlen et al., 2017; Zhang et al., 2017).”
The critical function of metabolic reprogramming in cancer metastasis
Xie, S., Pan, J., Xu, J., Zhu, W., & Qin, L. (2022) · Aging and Cancer · doi:10.1002/aac2.12044 · Cited by 13
Song, C., Yuan, Y., Zhou, J., He, Z., Hu, Y., Xie, Y., Liu, N., Wu, L., & Zhang, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.878937 · Cited by 13
Self-citationDebelenko, L. V., MANSUKHANI, M. M., & Remotti, F. (2023) · Pediatric and Developmental Pathology · doi:10.1177/10935266231152370 · Cited by 13
“Glu453Lys) variant has been identified in a variety of cancers.(7) Experimental studies in vitro and in vivo(12) demonstrated that heterozygous PIK3CA activation in stem cells leads to relatively mild biochemical and transcriptional consequences, which, however, have a cumulative effects promoting the sustained low-gr…”
BackgroundPIK3CA copy-number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancerPreprint
Amato, O., Buisseret, L., Gebhart, G., Plouznikoff, N., Larsimont, D., Awada, A. H., Piccart, M. J., & Aftimos, P. G. (2023) · Molecular Case Studies · doi:10.1101/mcs.a006255 · Cited by 15
“…impacts on PI3K protein expression and on phosphorAKT levels, whereas the OncoKB database lists the amplification as likely gain-of-function, providing rationale for a predictive value of CNAs for response to PI3K inhibitors (Chakravarty et al. 2017; Zhang et al. 2017; Smith and Sheltzer 2018).”
BackgroundPrognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma
Li, N., Chen, J., Liu, Q., Qu, H., Yang, X., Gao, P., Wang, Y., Gao, H., Wang, H., & Zhao, Z. (2021) · PeerJ · doi:10.7717/peerj.11901 · Cited by 12
Liang, W., Zhu, T., Tan, N., Jing, G., Xie, L., Dang, Y., & Li, Z. (2022) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2022.101479 · Cited by 12
Shen, W.-J., & Zhang, Y. (2024) · Discover Oncology · doi:10.1007/s12672-024-00875-8 · Cited by 12
Self-citationMa, J., Xue, K., Jiang, Y., Wang, X., He, D., & Guo, P. (2024) · Scientific Reports · doi:10.1038/s41598-024-66020-1 · Cited by 13
“Among them, the PI3K/AKT/mTOR pathway is one of the most important growth regulatory pathways in cancers 27 .”
BackgroundSun, C., Gui, J., Sheng, Y., Huang, L., Zhu, X., & Huang, K. (2025) · Discover Oncology · doi:10.1007/s12672-025-02592-2 · Cited by 12
“Indeed, mTOR signaling is activated in tumors generally, altering the expression levels or activities of critical metabolic factors in the pathway [209]. mTOR orchestrates tumor-related anabolic processes such as fatty acid, lipid synthesis, protein, and nucleotide while also governing PCD…”
Yang, Y., Fan, R., Zhang, B., & Liu, K. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06793-9 · Cited by 12
Beta-Elemene Reduces the Malignancy of Non-Small Cell Lung Cancer by Enhancing C3orf21 Expression
Cai, H., Ren, L., Wang, Y., & Zhang, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.571476 · Cited by 12
“It is well known that Cyclin D1, c-Myc and Cox2 can promote the proliferation of tumor cells (23) while PTEN can suppress the PI3K/AKT/mTOR signaling (24).”
BackgroundSelf-citationNRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells
Zhuang, W., Dong, X. D., Wang, B., Liu, N., Guo, H., Zhang, C., & Gan, W. (2021) · Oncology Letters · doi:10.3892/ol.2021.12940 · Cited by 12
“Moreover, studies have shown that metabolic changes, such as increased glucose or amino acid intake, can affect mTOR signaling (37,38).”
The Mechanisms of Ferroptosis and the Applications in Tumor Treatment: Enemies or Friends?
Tan, S., Kong, Y., Xian, Y., Gao, P., Xu, Y., Wei, C., Lin, P., Ye, W., Li, Z., & Zhu, X. M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.938677 · Cited by 14
Zhou, H., Yun, X., Shu, Y., & Xu, K. (2023) · Oncology Letters · doi:10.3892/ol.2023.13687 · Cited by 12
“A study that analyzed 32 cancer types in The Cancer Genome Atlas identified that KRAS exerts a pro‐tumorigenic effect via activation of the PI3K/AKT/mTOR pathway in pancreatic cancer (6).”
BackgroundGao, X., Hong, C., Xie, Y., & Zeng, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1103147 · Cited by 12
“As a downstream molecule of the PI3K/AKT pathway, mTOR signaling is commonly activated in tumors and controls cancer cell metabolism by altering expression and/or activity of a number of key metabolic enzymes (31).”
BackgroundHölzen, L., Mitschke, J., Schönichen, C., Hess, M. E., Ehrenfeld, S., Boerries, M., Miething, C., Brummer, T., & Reinheckel, T. (2022) · Theranostics · doi:10.7150/thno.68299 · Cited by 11
“This approach could be applied to other PI3K mutated cancers [5,9] or combined with other inhibitors [15], like Alpelisib [18], in the future.”
BackgroundXu, Z., Liu, L., Jiang, W., Qiu, Y., Zhang, B., Cheng, J., Luo, J., Guo, J., & Xu, J. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009963 · Cited by 11
Molefi, T., Mabonga, L., Hull, R., Mwazha, A., Sebitloane, M., & Dlamini, Z. (2025) · Cells · doi:10.3390/cells14050382 · Cited by 12
The role and research progress of serine metabolism in tumor cells
Lyu, H., Bao, S., Cai, L., Wang, M., Liu, Y., Sun, Y., & Hu, X. S. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1509662 · Cited by 13
“In various cancers, serine metabolism, one-carbon (1C) metabolism, and mTOR signaling pathways show abnormal hyperactivation (32, 122, 123).”
Self-citationHe, X., Yang, X., Xia, Q., Zhao, X., Li, S., He, X., Wang, R., & Wang, T. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.663262 · Cited by 11
“Furthermore, molecular changes in PI3K/AKT/mTOR pathway, containing mutations, copy number, protein, or RNA, have been detected in 11,219 human cancers (32 major cancer types included) (31).”
BackgroundDiscovering Synergistic Compounds with BYL-719 in PI3K Overactivated Basal-like PDXs
Boyd, D. C., Zboril, E. K., Olex, A. L., Leftwich, T. J., Hairr, N. S., Byers, H. A., Valentine, A. D., Altman, J. E., Alzubi, M. A., Grible, J. M., et al. (2023) · Cancers · doi:10.3390/cancers15051582 · Cited by 11
“To assess clinically actionable targets of these models, NGS was utilized to characterize pathogenic genetic profiles of 14 cell lines and 20 PDX samples (Table 1), which revealed pathogenic PIK3CA aberrations in 37% of models tested; 5 cell lines and 7 PDXs. PIK3CA was the second most commonly identified pathogenic d…”
BackgroundInfluentialGrowth Signaling Networks Orchestrate Cancer Metabolic NetworksPreprint
Manning, B. D., & Dibble, C. C. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041543 · Cited by 11
Hu, J., Guo, Y., Ren, L., Zhang, H., Qin, X., Yin, F., & Liu, X. (2026) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5c01372 · Cited by 13
Dong, J., Qian, Y., Zhang, W., Xu, J., Wang, L., Fan, Z., Jia, M., Wei, L., Yang, H., Luo, X., et al. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176401 · Cited by 10
Rational Design of a Novel 6 H -Benzo[ c ]chromen Series as Selective PI3Kα Inhibitors
Shi, X., Feng, H., Tian, H., Ma, H., Pang, X., Mao, C., Peng, X., Xu, Z., Han, W., Yan, Y., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00992 · Cited by 10
Targeting on the PI3K/mTOR: a potential treatment strategy for clear cell ovarian carcinoma
Zheng, K., Jin, G., Cao, R., Gao, Y., Xu, J., Chai, R., & Kang, Y. (2025) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-024-04748-3 · Cited by 11
“In cancer cells, mutations in AKT or alterations in mTORC1 activation enhance tumor cell growth, proliferation, and metastasis [38, 39].”
Huang, Y., Lu, H., Liu, Y. Z., Wang, J., Xia, Q., Shi, X., Jin, Y., Liang, X., Wang, W., Ma, X., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00359-z · Cited by 10
“In human cancer cells, mTOR is frequently activated and alters the activities of downstream targets, such as S6 kinases (S6K) and 4E-binding proteins (Alessi et al, 1997; Saxton and Sabatini, 2017; Zhang et al, 2017).”
Self-citationDeciphering molecular pathways in urological cancers: A gateway to precision therapeutics
Hushmandi, K., Farahani, N., Einollahi, B., Salimimoghadam, S., Alimohammadi, M., Liang, L., Liu, L., & Sethi, G. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.06.009 · Cited by 11
Broege, A., Rossetti, S., Sen, A., Forest, A. D. L., Davis, L., Seibel, M. I., Menon, A. S., Stokke, S., Macaulay, A., Molden, J. S., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125844 · Cited by 12
“In addition to canonical PIK3CA/PTEN genetic alterations, the increased activation of the PAM pathway in cancer cells can be caused by other genetic and non-Int genetic factors [1,68,69].”
Yang, J., Liu, Y., Lan, S., Yu, S., Ma, X., Luo, D., Shan, H., Zhong, X.-X., Yan, G., & Li, R. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00572 · Cited by 10
Self-citationPrecision Medicine: Progress, Pitfalls, and Promises
Pilie, P. G., LoRusso, P. M., & Yap, T. A. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0904 · Cited by 10
Fang, B., Kannan, A., Guo, T., & Gao, L. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.25488 · Cited by 10
“A recent study examining PI3K/Akt/mTOR pathway across more than 11, 000 human cancers representing 32 major types in the TCGA database has shown that a substantial fraction of cancers demonstrating high mTOR pathway activity[26].”
BackgroundYuan, Z., & Li, Z. (2020) · Translational Cancer Research · doi:10.21037/tcr.2019.12.47 · Cited by 10
“The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway has been reported to play a crucial role in a variety of malignancies (13-15), and some lncRNAs exert their cancer-related effects by regulating the PI3K/Akt pathway (5).”
BackgroundImamura, T., Okamura, Y., Ohshima, K., Uesaka, K., Sugiura, T., Ito, T., Yamamoto, Y., Ashida, R., Ohgi, K., Otsuka, S., et al. (2022) · Cancer Medicine · doi:10.1002/cam4.4571 · Cited by 9
Monti, M., Gatta, L. B., Bugatti, M., Pezzali, I., Picinoli, S., Manfredi, M., Lavazza, A., Vanella, V. V., Giorgis, V. D., Zanatta, L., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-023-04784-2 · Cited by 9
“In our SN-MM cohort, PI3K-Akt-mTOR pathway activation was also observed in MM cases lacking PIK3CA mutations and showing PTEN expression, indicating a complex genetic and epigenetic basis for this finding [16, 69].”
BackgroundChen, F., Zhang, Y., Shen, L., & Creighton, C. J. (2024) · Nature Communications · doi:10.1038/s41467-024-51276-y · Cited by 9
“This basic overall approach to pan-histology genomic analysis derives inspiration from pan-cancer studies of adult cancers of various tissues of origin, including large-scale efforts from The Cancer Genome Atlas (TCGA) 13,28,39 and the Pan-Cancer Analysis of Whole Genomes (PCAWG) 14 .”
Self-citationSinnarkar, S., Suryawanshi, P. V., Dilip, A., Bhawalkar, J., & Ladke, V. S. (2024) · Journal of the Egyptian National Cancer Institute · doi:10.1186/s43046-024-00246-y · Cited by 10
“Alterations and mutations in the PTEN/PI3K/AKT/mTOR pathway enhance cellular proliferation and diminish apoptosis [39].”
Li, G., Su, X., Yang, Y., Li, D., Cui, Z., Deng, X., Hu, P., & Hu, L. (2025) · Communications Biology · doi:10.1038/s42003-025-08265-8 · Cited by 9
“Our analysis reveals that four pathways are closely associated with pan-cancer: Focal adhesion 59 , Endocrine resistance 60 , PI3K-Akt signaling pathway 61 , and Proteoglycans in cancer 62 .”
Tamoxifen induces PI3K activation in uterine cancer
Kübler, K., Nardone, A., Anand, S. K., Gurevich, D., Gao, J., Droog, M., Hermida‐Prado, F., Akhshi, T. K., Feiglin, A., Feit, A. S., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02308-w · Cited by 9
“1g), distinguishing these two genes, especially PIK3CA , from other PI3K pathway genes 37 in TA-UC (Extended Data Fig.”
InfluentialIFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway
Shi, X. Y., Zhang, X.-L., Shi, Q.-Y., Qiu, X., Wu, X., Zheng, B.-L., Jiang, H., & Qin, S. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02748-w · Cited by 9
“In the AKT/ mTOR pathway, AKT inhibits cell apoptosis and promotes cell proliferation by activating the protein mTOR [25].”
BackgroundLee, W. K., Park, S., Lee, S. G., Jeong, S., Lee, G., Ryu, D., Schoonjans, K., Auwerx, J. H., Lee, J., & Jo, Y. S. (2022) · Oncogene · doi:10.1038/s41388-022-02484-7 · Cited by 10
“To overcome this problem, we analysed the role of MSR and the mechanism coupling the MSR to mTOR signalling in a cohort of patients from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA), since thyroid cancers harbour homogenous driver mutations and have a lower somatic mutation and genetic alteration burden than oth…”
MethodSelf-citationProteogenomics in Cancer: Then and Now
Wang, X., Xu, Y., & Lau, A. T. Y. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.3c00196 · Cited by 10
TAS0612, a Novel RSK, AKT, and S6K Inhibitor, Exhibits Antitumor Effects in Preclinical Tumor Models
Ichikawa, K., Ito, S., Kato, E., Abe, N., Machida, T., Iwasaki, J., Tanaka, G., Araki, H., Wakayama, K., Jona, H., et al. (2023) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-1037 · Cited by 9
Zhao, X., Cai, X., Zhu, H., Dang, Q., Yang, Q., Zhu, Y., Zhang, Y., Zhang, M., Jiang, X., Hu, Z., et al. (2024) · Archives of Toxicology · doi:10.1007/s00204-023-03664-4 · Cited by 9
“The PI3K/AKT/mTOR signaling pathway participates in cell metabolism, growth, migration, survival and angiogenesis (Rodon et al. 2013) and is known to promote the growth and survival of tumor cells (Zhang et al. 2017).”
Self-citationRegulatory-Associated Protein of mTOR-Mediated Signaling: A Nexus Between Tumorigenesis and Disease
Chouhan, S., Kumar, A., Piprode, V., Dasgupta, A., Singh, S., & Khalique, A. (2024) · Targets · doi:10.3390/targets2040020 · Cited by 10
“The link between mTOR and cancer has garnered significant attention, as aberrant mTOR activation is frequently observed in tumorigenesis [28,29].”
Shimizu, S., Sakamoto, S., Fukuda, A., Yanagi, Y., Uchida, H., Takeda, M., Yamada, Y., Nakano, N., Yoshioka, T., & Kasahara, M. (2020) · American Journal of Transplantation · doi:10.1111/ajt.15978 · Cited by 9
Takahashi, N., Hatakeyama, K., Nagashima, T., Ohshima, K., Urakami, K., Yamaguchi, K., & Hirashima, Y. (2021) · International Journal of Gynecological Cancer · doi:10.1136/ijgc-2021-002983 · Cited by 9
Liu, P. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2021.798748 · Cited by 9
“, TP53, RB1), Wnt/β-catenin, andMYC (Chen et al., 2017; Zhang et al., 2017; Chen et al., 2018).”
Nam, S., & Lee, Y. (2022) · Cancers · doi:10.3390/cancers14092340 · Cited by 9
Samaratunga, H., Egevad, L., Thunders, M. C., Iczkowski, K. A., van der Kwast, T., Kristiansen, G., Pan, C., Leite, K. R. M., Evans, A. J., Clouston, D. R., et al. (2022) · Pathology · doi:10.1016/j.pathol.2022.09.002 · Cited by 9
Arribas, A. J., Napoli, S., Gaudio, E., Herbaux, C., Cannas, E., Tarantelli, C., Pittau, R. B., Cascione, L., Munz, N., Aresu, L., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023012291 · Cited by 13
“Furthermore, the transcripts higher in the resistant than in the parental SU-DHL-4 were enriched in the gene expression signatures of sensitivity to PI3K inhibitors 43,44 (supplemental Figure 24).”
Pan, J., Yan, D., Liang, Y., Yang, L., Hu, C., & Chen, M. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.137184 · Cited by 9
Self-citationMAGE-A4 induces non–small cell lung cancer and tumor-promoting plasma cell accumulation
Armstrong, D., Chang, C.-Y., Hong, M. J., Green, L., Shen, Y., Hudson, W., Mauk, K. E., Song, L., Jammi, S., Casal, B., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads4227 · Cited by 9
Self-citationGinkgolide B Inhibits EMT and Promotes Pyroptosis in Gastric Cancer via AKT/mTOR Pathway
Lu, X., Zhang, Y., Wang, R., & Li, Z. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s485240 · Cited by 8
“37,38 42 Our results indicated that GGB deactivated the PI3K/AKT/m-TOR pathway in a dose-dependent manner, thereby inhibiting proliferation and promoting apoptosis and pyroptosis.”
Self-citationElkholi, I. E., Robert, A., Malouf, C., Wu, J., Kuasne, H., Drápela, S., MacLeod, G. D. A. H., Hébert, S., Pacis, A., Calderon, V., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-23-2654 · Cited by 8
“Despite the high sequencing coverage (see 271 Supplementary Methods), no differential genomic alterations of established functional 272 consequences in the Pi3k-Akt-mTORC1 pathway genes (29) were found between the two cell lines 273 to explain the revealed differential dependence and signaling activity (Fig 3D).”
Leiphrakpam, P. D., Batra, R., Tenner, L. L., & Are, C. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl39100 · Cited by 10
Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling
Bissegger, L., Constantin, T. A., Keleş, E., Raguž, L., Barlow-Busch, I., Orbegozo, C., Schaefer, T., Borlandelli, V., Bohnacker, T., Sriramaratnam, R., et al. (2024) · Chemical Science · doi:10.1039/d4sc05459h · Cited by 9
“26 Despite its well-known oncogenic role, the current understanding of PI3K a isoform-speci c contributions in cellular signaling events and disease mechanisms remains poor.”
AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis
McRee, S. K., Bayer, A. L., Pietruska, J. R., Tsichlis, P. N., & Hinds, P. W. (2023) · Cancers · doi:10.3390/cancers15204958 · Cited by 8
“…alterations; the activation of mutations or gene amplification of AKT1 and AKT2 are more common in BRAF V600E mutant and PTEN-null melanomas [28,29], whereas AKT3 amplification is more common in BRAF WT PTEN WT tumors [26], although AKT3 has also demonstrated co-operativity with BRAF V600E to…”
BackgroundGupta, A., & Stocker, H. (2020) · eLife · doi:10.7554/elife.53159 · Cited by 8
NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma
Feng, H., Cao, S., Fu, S., Liu, J., Gao, Y., Dong, Z., Cai, T., Wen, L., Xiong, Z., Li, S., et al. (2024) · The Journal of Pathology · doi:10.1002/path.6340 · Cited by 7
“Additionally, considering the important role of these pathways in normal tubular epithelial cells and other normal cells [41,42], targeting these pathways may exhibit toxicity toward normal tissues.”
Broege, A., Rossetti, S., Sen, A., Menon, A. S., MacNeil, I. A., Molden, J. S., & Laing, L. G. (2024) · Cancers · doi:10.3390/cancers16203520 · Cited by 9
“Dysregulation of the PAM pathway can also occur in the absence of canonical PAM pathway mutations, e.g., due to the dysregulation of interconnected pathways (e.g., RTKs), or epigenetic mechanisms [5,9,10].”
BackgroundMahmood, N. H., & Kadir, D. H. (2025) · Cihan University-Erbil Scientific Journal · doi:10.24086/cuesj.v9n1y2025.pp14-23 · Cited by 7
Zhang, Y., Chen, F., & Creighton, C. J. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-01029-x · Cited by 7
“We have utilized this pan-cancer analysis approach to identify molecular survival correlates for gene subsets or gene signatures in the TCGA cohort and other cohorts 10,13,22,25,26 .”
InfluentialSelf-citationID2 promotes tumor progression and metastasis in thyroid cancer
Deng, Z., Xu, M., Ding, Z., Kong, J., Liu, J., Zhang, Z., & Cao, P. (2024) · Endocrine · doi:10.1007/s12020-023-03674-3 · Cited by 7
“PI3K/Akt pathway [19, 20] is intricately associated with the initiation and progression of tumors, as well as the development of treatment resistance and recurrence.”
BackgroundDsouza, N. R., Cottrell, C. E., Davies, O. M. T., Tollefson, M. M., Frieden, I. J., Basel, D., Urrutia, R. A., Drolet, B. A., & Zimmermann, M. T. (2024) · Life · doi:10.3390/life14030297 · Cited by 7
Wu, P., Wang, X., Ma, Y., Xu, X., Liu, W., Sheng, Z., Chen, M., Zhou, R., Zhang, K., Goodin, S., et al. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104022 · Cited by 7
Mannella, V., Boehm, K., Celik, S., Ali, T., Mirza, A. N., Hasnaouy, M. E., Kaffa, A., Lyu, Y., Golahmadi, D. K., Leigh, I. M., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073567 · Cited by 7
A forward genetic screen identifies modifiers of rocaglate responsiveness
Shen, L. L., Pugsley, L., Cencic, R., Wang, H., Robert, F., Naineni, S. K., Sahni, A., Morin, G., Zhang, W., Nijnik, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-97765-8 · Cited by 7
“eIF4F consists of (1) an eIF4E subunit which specifically recognizes cap structures, (2) an eIF4A DEAD-box RNA helicase, and (3) a multi-domain scaffolding protein, eIF4G.”
BackgroundThe Interplay Between the Transcriptomics and Proteomics Profiles
Teibo, J. O., Silvestrini, V. C., Vargas, A. P., Lanfredi, G. P., & Faça, V. M. (2022) · Springer eBooks · doi:10.1007/978-3-030-87821-4_8 · Cited by 7
Kim, T. R., Jeong, H.-H., & Sohn, K.-A. (2019) · BMC Medical Genomics · doi:10.1186/s12920-019-0511-x · Cited by 7
Tian, W., Sun, L., Zhang, Q., Zhao, J., Guo, Y., Zhong, W., Liu, L., Meirelles, K., Tang, S., Zhang, J., et al. (2022) · Molecular Genetics and Genomics · doi:10.1007/s00438-022-01853-x · Cited by 7
“H1047R, had the highest effects in enzymatic activation (Burke et al. 2012; Zhang et al. 2017) and are not compatible with life for germline transmission (Mitchell and Phillips 2019).”
BackgroundSelf-citationIlozumba, M. N., Yao, S., Llanos, A. A. M., Omilian, A. R., Zhang, W., Datta, S., Hong, C., Davis, W., Khoury, T., Bandera, E. V., et al. (2022) · Discover Oncology · doi:10.1007/s12672-022-00497-y · Cited by 7
Chu, J., Yuan, C., Zhou, L., Zhao, Y., Wu, X., Yan, Y., Liu, Y., Liu, X., Jing, L., Dong, T., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35490 · Cited by 6
“The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, also known as the PAM signaling pathway, is involved in various physiological processes and plays a crucial role in the development of many diseases, especially cancer [15].”
BackgroundSelf-citationBerezovsky, A. D., Nuga, O., Datta, I., Bergman, K., Sabedot, T. S., Gurdziel, K., Irtenkauf, S. M., Hasselbach, L. A., Meng, Y., Mueller, C., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0315171 · Cited by 8
Xu, W., Li, X., He, F., Zhao, H., Wu, J., Li, M., Dai, X., Li, Y., Hu, X., Li, X., et al. (2025) · Nanoscale Advances · doi:10.1039/d5na00009b · Cited by 7
“9 12 Among the three branches of the UPR, the PERK pathway is the most easily activated.”
Synergistic inhibitory effect of α-humulene and sclareol on human pancreatic cancer cells
Kang, Y., Wang, X., Wei, X., Li, D., Gan, L., Jin, J., Wu, R., Wu, P., Sheng, Z., Zhang, K., et al. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.104958 · Cited by 6
AKT Isoforms as a Target in Cancer and Immunotherapy
Smit, D. J., & Jücker, M. (2022) · Current topics in microbiology and immunology · doi:10.1007/978-3-031-06566-8_18 · Cited by 7
Chantree, P., Martviset, P., Sornchuer, P., Thongsepee, N., Sangpairoj, K., Meemon, K., Niamnont, N., Tamtin, M., & Sobhon, P. (2023) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2023.28.1.69 · Cited by 6
“The progression of tumors, including cell proliferation, neovascularization, invasion, and migration, is facilitated by the PI3K/AKT/mTOR signaling pathway (Popolo et al., 2017; Zhang et al., 2017).”
BackgroundYang, Q., Cao, C., Wu, B., Yang, H., Tan, T., Shang, D., Xu, C. S., & Huang, X. (2024) · Cancers · doi:10.3390/cancers16030590 · Cited by 6
Basho, R. K., Zhao, L., White, J. B., Huo, L., Bassett, R. L., Mittendorf, E. A., Thompson, A., Litton, J. K., Ueno, N. T., Arun, B., et al. (2024) · JCO Precision Oncology · doi:10.1200/po.23.00124 · Cited by 6
Self-citationPredicting mechanism of action of cellular perturbations with pathway activity signatures
Ren, Y., Sivaganesan, S., Clark, N. A., Zhang, L., Biesiada, J., Niu, W., Plas, D. R., & Medvedovic, M. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa590 · Cited by 6
Ni, Z., Xu, S., Yu, Z., Ye, Z., Li, R., Chen, C., Yang, J., Liu, H., Zhou, Z., & Zhang, X. (2022) · Investigational New Drugs · doi:10.1007/s10637-022-01268-w · Cited by 6
Ladke, V. S., Kumbhar, G. M., Joshi, K., & Kheur, S. M. (2022) · Journal of Oral Biosciences · doi:10.1016/j.job.2022.09.002 · Cited by 9
Chicco, D., Alameer, A., Rahmati, S., & Jurman, G. (2022) · BioData Mining · doi:10.1186/s13040-022-00312-y · Cited by 6
“PIK3R2 belongs to a family of genes known to be involved in pan-cancer [73].”
BackgroundOh, K. S., Bahmad, H. F., Stoyanov, K. V., Amjad, I. H., & Brathwaite, C. D. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45020110 · Cited by 6
Metadata
- Authors
- Zhang, Y., Kwok-Shing Ng, P., Kucherlapati, M., Chen, F., Liu, Y., Tsang, Y. H., de Velasco, G., Jeong, K. J., Akbani, R., Hadjipanayis, A., Pantazi, A., Bristow, C. A., Lee, E., Mahadeshwar, H. S., Tang, J., Zhang, J., Yang, L., Seth, S., Lee, S., Ren, X., Song, X., Sun, H., Seidman, J., Luquette, L. J., Xi, R., Chin, L., Protopopov, A., Westbrook, T. F., Shelley, C. S., Choueiri, T. K., Ittmann, M., Van Waes, C., Weinstein, J. N., Liang, H., Henske, E. P., Godwin, A. K., Park, P. J., Kucherlapati, R., Scott, K. L., Mills, G. B., Kwiatkowski, D. J., & Creighton, C. J.
- Affiliations
- Baylor College of Medicine (US)
- Brigham and Women's Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Broad Institute (US)
- University of Wisconsin–Madison (US)
- Dana-Farber Cancer Institute (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Mills, Gordon B.
- Kwiatkowski, David J.
- Creighton, Chad J.
- ORCID
- Zhang, Yiqun
- Kucherlapati, Melanie
- Chen, Fengju
- Liu, Yuexin
- Tsang, Yiu Huen
- Jeong, Kang Jin
- Akbani, Rehan
- Hadjipanayis, Angela
- Pantazi, Angeliki
- Bristow, Christopher A.
- Lee, Eunjung
- Zhang, Jianhua
- Yang, Lixing
- Seth, Sahil
- Lee, Semin
- Song, Xingzhi
- Seidman, Jonathan
- Luquette, Lovelace J.
- Xi, Ruibin
- Protopopov, Alexei
- Westbrook, Thomas F.
- Shelley, Carl Simon
- Choueiri, Toni K.
- Ittmann, Michael
- Weinstein, John N.
- Liang, Han
- Henske, Elizabeth P.
- Godwin, Andrew K.
- Park, Peter J.
- Mills, Gordon B.
- Kwiatkowski, David J.
- Creighton, Chad J.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 31
- Issue
- 6
- Pages
- 820-832.e3
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC5502825
- OpenAlex
- W2616761213
- Semantic Scholar
- 1ca50d3272a9c1aa38b714579d66b2dff0588a2d
- Cited by
- 626
- References
- 45
- Citations by year
- 2026: 29 · 2025: 59 · 2024: 84 · 2023: 83 · 2022: 80 · 2021: 84 · 2020: 93 · 2019: 61 · 2018: 44 · 2017: 7
- FWCI
- 23.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (RP120713 C2, 5P50CA098258, 5U01CA168394)
- NIH (U24CA143883, 2P50CA101942-11A1, 1R21CA191687, 5P01CA120964, CA175486, CA209851, P30CA125123)
- Cancer Center (P30CA016672)
- Abbvie
- Adelson Medical Research Foundation
- AstraZeneca
- Breast Cancer Research Foundation
- Critical Outcomes Technology
- Horizon Diagnostics
- Illumina
- Ionis
- Karus Therapeutics
- Komen Research Foundation
- Nanostring
- Pfizer
- Takeda/Millennium Pharmaceuticals
- Tesaro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- PI3K/AKT/mTOR pathway, somatic mutations, copy number alterations, PTEN, STK11, structural variants, IDH1 mutation, VHL mutation, mutational hotspots
- MeSH terms
- Proteogenomics, Humans, Mutation, Neoplasms, Signal Transduction, Survival Analysis, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Databases, Genetic, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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