Cited by 248Neuroblastoma Research and TreatmentsPI3K/AKT/mTOR signaling in cancerNeurofibromatosis and Schwannoma Cases

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PI3King the Lock: Targeting the PI3K/Akt/mTOR Pathway as a Novel Therapeutic Strategy in Neuroblastoma

King, David, Yeomanson, Daniel, Bryant, Helen E.·2015·Journal of Pediatric Hematology/Oncology

DOI 10.1097/mph.0000000000000329

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Abstract

Neuroblastoma is the most common extracranial cancer in childhood. High-risk neuroblastoma continues to have a poor prognosis and there is an urgent need to design biologically based therapies that specifically target the pathways responsible for malignant transformation and progression. One such pathway is the PI3K/Akt/mTOR pathway. In this article we outline the evidence for aberrant activation of the PI3K/Akt/mTOR pathway in neuroblastoma and discuss the possible mechanisms which mediate it. We also discuss the development of treatments targeting this pathway in neuroblastoma and the challenges that must be overcome before such treatments can enter routine clinical practice.

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Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer.
Brodeur (2003)
Unresolved
Development of treatment strategies for advanced neuroblastoma. Int J Clin Oncol.
Hara (2012)
Unresolved
. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol.
Cohn (2009)
Unresolved
. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature.
Whitman (1985)
Unresolved
PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol.
Vanhaesebroeck (2012)
Unresolved
. Dissecting the PI3K signaling axis in pediatric solid tumors: novel targets for clinical integration. Front Oncol.
Loh (2013)
Unresolved
Overcoming acquired resistance to anticancer therapy: focus on the PI3KAKTmTOR pathway. Cancer Chemother Pharmacol.
Burris (2013)
Unresolved
. N-myc is a novel regulator of PI3K-mediated VEGF expression in neuroblastoma. Oncogene.
Kang (2008)
Unresolved
. Activation of Akt predicts poor outcome in neuroblastoma. Cancer Res.
Opel (2007)
Unresolved
. Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo. Oncogene.
Johnsen (2008)
Unresolved

Show all 52 references

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“In addition, the inhibition of pro-apoptotic factors such as Bad and FOXO transcription factors decreased apoptotic changes.(25) The above-mentioned factors are thought to participate in different cell activities (Fig.”
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Background
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Background
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“This pathway can serve as a therapeutic target for NB 62,63 .”
Background
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“22 25 Chemotherapy used in the treatment of NB has seldom changed over time, however recent genomic advances have allowed for targeted therapies to become more readily integrated into chemotherapy regimens to improve patient outcomes.”
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Background
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“We then assessed the impact of low-frequency rMS on the JNK/p38/ERK and PI3K/AKT/ mTOR pathways, which are related to unlimited cell proliferation, dedifferentiation, and a lack of tumor apoptosis [36,37].”
CFNC, a neocryptolepine derivative, inhibited the growth of gastric cancer AGS cells by inhibiting PI3K/AKT signaling pathway
Ma, Y., Xu, H., Zhou, Z., Tian, Y., Du, K., Zhang, H., Jiang, X., Lu, J., Niu, Y., Tu, L., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175408 · Cited by 7
Integrative Analyses of Transcriptome Sequencing Identify Functional miRNAs in the Chicken Embryo Fibroblasts Cells Infected With Reticuloendotheliosis Virus
Zhai, J., Gao, C., Fu, L., et al. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00340 · Cited by 7
“Reports showed that the PDPK1/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle (Rafalski and Brunet, 2011; King et al., 2015).”
Targeting Functional Activity of AKT Has Efficacy against Aggressive Neuroblastoma
Grand, M. L., Kimpton, K., Gana, C. C., Valli, E., Fletcher, J. I., & Kavallaris, M. (2020) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00085 · Cited by 7
Identification of interactive molecules between antler stem cells and dermal papilla cells using an in vitro co-culture system
Sun, H., Sui, Z., Wang, D., Ba, H., Zhao, H., Zhang, L., & Li, C. (2019) · Journal of Molecular Histology · doi:10.1007/s10735-019-09853-9 · Cited by 7
The Role of Connections Between Cellular and Tissue Mechanical Elements and the Importance of Applied Energy in Mechanotransduction in Cancerous Tissue
Silver, F. H. (2025) · Biomolecules · doi:10.3390/biom15040457 · Cited by 6
“A recent review suggests that the PAM axis is the most frequently activated signaling pathway in human cancer [76], and crosstalk between the PAM, MAPK, and WNT/beta-catenin pathways has been reported to be responsible for controlling critical functions in human cancer cells [77].”
Mangiferin Against Respiratory Diseases: Pharmacological Targets and Prospects
Ahmed, K. A., Afrin, N., Ghosh, P., Heya, I. A., Akash, S. R., Moni, A., Islam, M. N., Hossain, M. G., Sinopoli, A., Hannan, M. A., et al. (2025) · Pharmacology Research & Perspectives · doi:10.1002/prp2.70163 · Cited by 7
“It is intricately associated with processes including cancer formation, cell qui-escence, and proliferation [139].”
Efficacy of combined targeted therapy with PI3K and CDK4/6 or PARP and WEE1 inhibitors in neuroblastoma cell lines
Lukoseviciute, M., Holzhauser, S., Pappa, E., Mandal, T., Dalianis, T., & Kostopoulou, O. N. (2023) · Oncology Reports · doi:10.3892/or.2023.8603 · Cited by 6
“Moreover, PI3K/Akt is activated in several tumor types, including NB (16,17).”
Background
Promoter hypomethylated PDZK1 acts as a tumorigenic gene in glioma by interacting with AKT1
Ren, X., Deng, D., Xiang, S., & Feng, J. (2024) · Aging · doi:10.18632/aging.205750 · Cited by 6
Neuroblastoma Cell Death Induced by eEF1A2 Knockdown Is Possibly Mediated by the Inhibition of Akt and mTOR Phosphorylation
Khwanraj, K., & Dharmasaroja, P. (2021) · International Journal of Hematology-Oncology and Stem Cell Research · doi:10.18502/ijhoscr.v15i4.7477 · Cited by 6
Exosomal microRNA-20b-5p contributes to cytarabine resistance in acute myeloid leukemia via the microtubule-associated serine/threonine kinase-like–phosphatidylinositol 3-kinase–protein kinase B signaling axis
Huang, A., Wang, L., Chen, Y., Zhao, Z., Cheng, W., Cheng, W., Cheng, B., Guo, H., Li, Y., Cai, J., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.148750 · Cited by 5
The Role and Mechanism of Innate Immune Regulation in Overcoming Oxaliplatin Resistance and Enhancing Anti-Tumor Efficacy in Colorectal Cancer
Wang, X., Xi, M., Lu, X., & Tan, X. (2025) · Pharmaceuticals · doi:10.3390/ph18030317 · Cited by 5
“The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway has been investigated extensively to determine its role in drug resistance and driving malignancy processes in solid cancer patients [39–43].”
IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug’s Targeted Cerebral Ischemic Networks
Wang, P., Yu, Y., Liu, J., Li, B., Zhang, Y., Li, D., Xu, W., Liu, Q., & Wang, Z. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.637253 · Cited by 6
“For example, inhibition of MAPK signaling or mTOR signaling can effectively reduce cerebral ischemia reperfusion injury (Dennis et al., 2001; Sovan, 2013; Johansson et al., 2014; King et al., 2015; Yang et al., 2016).”
Background
The Potential for Natural Products to Overcome Cancer Drug Resistance by Modulation of Epithelial-Mesenchymal Transition
Ghalehno, A. D., Boustan, A., Abdi, H., Aganj, Z., Mosaffa, F., & Jamialahmadi, K. (2022) · Nutrition and Cancer · doi:10.1080/01635581.2021.2022169 · Cited by 5
“These include the PI3K-Akt, RAS-RAF-MEK-ERK, SRC, JAK-STAT signaling pathways (59).”
Background
Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches
Pirvu, L. C., Neagu, G., Albulescu, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087404 · Cited by 5
“This way, clinical data appear to converge on the following feasible molecular targets: the tropomyosin kinase receptor homologs A, B and C (Trk) which control the spatiotemporal regulation of growth, differentiation, and survival of central and peripheral neurons [10]; the mammalian target of rapamycin (mTOR), a seri…”
BackgroundInfluential
Exploring the Functional Mechanism of Action of Sanxiankaixin Powder in Preventing and Treating Reproductive Aging Based on Network Pharmacology and Molecular Docking
Liu, Z., Li, Z. A., Sun, Y., Zhao, F., Chen, S., Zhao, Y., Zhang, Z., Liao, Z., & Geng, Q. (2024) · Integrative Medicine in Nephrology and Andrology · doi:10.1097/imna-d-24-00022 · Cited by 5
“[73] It is involved in regulating cell activation, proliferation, metabolism, inflammation, and apop - tosis.”
Applications and prospects of targeted therapy for neuroblastoma
Wang, J., Yao, W., & Li, K. (2020) · World Journal of Pediatric Surgery · doi:10.1136/wjps-2020-000164 · Cited by 5
Nuclear Factor-κB Activating Protein Plays an Oncogenic Role in Neuroblastoma Tumorigenesis and Recurrence Through the Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway
Liu, J., Zhang, M.-Y., Kan, Y., Wang, W., Liu, J., Gong, J.-H., & Yang, J.-G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.622793 · Cited by 5
“Knockdown of Nuclear Factor-κB Activating Protein Inhibited the Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway in SK-N-SH Cells The PI3K/AKT signaling pathway is an important signaling pathway involved in various malignant tumors, including NB (King et al., 2015).”
Method
The cyclin dependent kinase inhibitor p21Cip1/Waf1 is a therapeutic target in high-risk neuroblastoma
Sorteberg, A. L., Halipi, V., Wickström, M., & Fard, S. S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.906194 · Cited by 5
In silico analysis and prediction of transcription factors of the proteins interacting with astrocyte elevated gene-1
Sriramulu, S., Nandy, S. K., Ganesan, H., et al. (2021) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2021.107478 · Cited by 5
Molecular mechanisms and signaling pathways involved in immunopathological events of COVID-19
Peyvandi, A. A., Niknazar, S., Mehrjerdi, F. Z., Abbaszadeh, H., Khoshsirat, S., & Peyvandi, M. (2021) · Physiology and Pharmacology · doi:10.52547/ppj.25.3.193 · Cited by 5
Targeting long non-coding RNA HERC2P3 inhibits cell growth and migration in human gastric cancer cells.
Chen, J., Cai, H., Xie, Y., et al. (2017) · PubMed · Cited by 4
Effects of Monensin and Rapamycin Combination Therapy on Tumor Growth and Apoptosis in a Xenograft Mouse Model of Neuroblastoma
Koçoğlu, S. S., Sunay, F. B., & Akkaya, P. N. (2023) · Antibiotics · doi:10.3390/antibiotics12060995 · Cited by 4
“examined activation of the PI3K pathway in 39 samples from patients with high-risk neuroblastoma and showed that expression of PI3Kp110 and PI3Kp85 could be detected in the cytoplasm of 54% of cases, and phosphorylated AKT was present in the cytoplasm in almost all cases [29].”
Method
Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway
Fan, X.-P., Wang, J., Chen, S.-Y., Li, X., Cao, J., Wang, H., Ding, L., Che, T., & Li, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-89217-4 · Cited by 5
“AKT, a crucial serine/threonine kinase and pivotal component of the PI3K signaling pathway, is essential for functions like cell growth, programmed cell death, movement, glucose regulation, and gene expression 54 .”
Cytotoxic lycorine alkaloids of the plant family Amaryllidaceae
Nair, J. J., & Staden, J. V. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108619 · Cited by 4
MicroRNAs and their target mRNAs as potential biomarkers among smokers and non-smokers with lung adenocarcinoma
Malik, S. K., Paracha, R. Z., Khalid, M., et al. (2018) · IET Systems Biology · doi:10.1049/iet-syb.2018.5040 · Cited by 4
The potential mechanism of the Ruhao Dashi formula in treating acute pneumonia via network pharmacology and molecular docking
Yi, X.-X., Zhou, H., He, Y. T., Yang, C., Yu, L., Wan, H., & Chen, J. (2023) · Medicine · doi:10.1097/md.0000000000033276 · Cited by 4
Characteristic Mutational Damages in Gastric and Colorectal Adenocarcinomas
Yermekova, S., Orazgaliyeva, M., Goncharova, T., Rakhimbekova, F., Kaidarova, D. R., & Shatkovskaya, O. (2023) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2023.24.11.3939 · Cited by 4
“Another RAS-activated signalling pathway is the PI3K/AKT/mTOR pathway, which stimulates protein synthesis, cell growth, and inhibits apoptosis (King et al., 2015).”
Background
Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth
Wang, K., Liao, P.-Y., Chang, W., Yang, C.-R., Su, Y., Wu, P., Wu, Y., Hung, Y., Akhtar, N., Lai, H., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1281067 · Cited by 4
Unravelling the novel insights between miR-7 and Parkinson’s disease (PD)
Kushwaha, S., Lakhanpal, V., Elangovan, A., Iyer, M., Kinoshita, M., Narayanasamy, A., HariKrishnaReddy, D., Siama, Z., Yadav, M. K., & Vellingiri, B. (2026) · Neurological Sciences · doi:10.1007/s10072-026-08834-7 · Cited by 3
“When PI3K is activated, AKT is phosphorylated and activated, and then it localizes to the cellular membrane [93].”
Association of PI3K/AKT/mTOR Pathway with Cancer and Its Therapeutic Implications
Saleem, S., Bashir, I., Khan, M. S., & Ahanger, M. S. (2025) · Springer eBooks · doi:10.1007/978-981-96-2763-9_3 · Cited by 3
Establishment of a mouse model for injury-induced scar formation and the accompanying chronic pain: Comprehensive microarray analysis of molecular expressions in fibrosis and hyperalgesia
Li, Y., Iida, H., Kimata, K., Zhuo, L., Ota, A., Kimura, S. H., Yin, X., Deie, M., & Ushida, T. (2019) · Molecular Pain · doi:10.1177/1744806919892389 · Cited by 3
“In many cancers, this pathway is overactive, which reduces apoptosis and allows cell proliferation.(40) However, this pathway is important to promote growth and proliferation over differentiation of adult stem cells, specifically neural stem cells.”
Background
The Importance of RTK Signaling Genes and their Inhibitors in Breast Cancer
Rahimi, M., Kakroodi, S. T., & Tajvidi, M. (2022) · Journal of Obstetrics Gynecology and Cancer Research · doi:10.30699/jogcr.7.4.258 · Cited by 3
“This pathway is vital in the cell processes, such as cell division, growth, survival, and angiogenesis (11, 12).”
Background
Specific Inhibition of GSK-3β by Tideglusib: Potential Therapeutic Target for Neuroblastoma Cancer Stem CellsPreprint
Bahmad, H. F., Chalhoub, R., Harati, H., Bou-Gharios, J., Ballout, F., Monzer, A., Msheik, H., Assi, S., Araji, T., Elajami, M. K., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.18.953596 · Cited by 3
Alfaxalone activates Human Pregnane-X Receptors with greater efficacy than Allopregnanolone: an in-vitro study with implications for neuroprotection during anesthesiaPreprint
Serrao, J. M., & Goodchild, C. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.05.284075 · Cited by 4

Authors: King, D., Yeomanson, D., & Bryant, H. E.
Affiliations: Sheffield Children's Hospital (GB)
ORCID: King, David
Bryant, Helen E.
Venue: Journal of Pediatric Hematology/Oncology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-05
Volume: 37
Issue: 4
Pages: 245-251
ISSN: 1077-4114 (ISSN-L)
DOI: 10.1097/mph.0000000000000329
OpenAlex: W1974245465
Cited by: 248
References: 52
Citations by year: 2026: 10 · 2025: 19 · 2024: 31 · 2023: 24 · 2022: 26 · 2021: 29 · 2020: 29 · 2019: 25 · 2018: 22 · 2017: 22 · 2016: 11
FWCI: 2.46
Type: journal article
Language: en
Open access: closed
Locations: Journal of Pediatric Hematology/Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
Keywords: neuroblastoma, PI3K/AKT/mTOR pathway, high-risk neuroblastoma, PI3K inhibitors, AKT inhibitors, mTOR inhibitors, targeted therapy, childhood cancer
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Phosphoinositide-3 Kinase Inhibitors, Animals, Humans, Neuroblastoma, Signal Transduction, Phosphatidylinositol 3-Kinases, Multiprotein Complexes, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases

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PI3King the Lock: Targeting the PI3K/Akt/mTOR Pathway as a Novel Therapeutic Strategy in Neuroblastoma

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