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

Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer.

Brodeur (2003)

Development of treatment strategies for advanced neuroblastoma. Int J Clin Oncol.

Hara (2012)

. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol.

Cohn (2009)

. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature.

Whitman (1985)

PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol.

Vanhaesebroeck (2012)

. Dissecting the PI3K signaling axis in pediatric solid tumors: novel targets for clinical integration. Front Oncol.

Loh (2013)

Overcoming acquired resistance to anticancer therapy: focus on the PI3KAKTmTOR pathway. Cancer Chemother Pharmacol.

Burris (2013)

. N-myc is a novel regulator of PI3K-mediated VEGF expression in neuroblastoma. Oncogene.

Kang (2008)

. Activation of Akt predicts poor outcome in neuroblastoma. Cancer Res.

Opel (2007)

. Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo. Oncogene.

Johnsen (2008)

. Analysis of PI3KAKTmTOR signalling pathway in high risk neuroblastic tumours. Pol J Pathol.

Izycka-Swieszewska (2010)

. Mutations in PIK3CA are infrequent in neuroblastoma. BMC Cancer.

Dam (2006)

. Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res.

Shukla (2012)

. Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines. Int J Cancer.

Munoz (2004)

. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell.

Berry (2012)

. Oncogenic mutations of ALK kinase in neuroblastoma. Nature.

Chen (2008)

. Genetic and pharmacologic identification of Akt as a mediator of brain-derived neurotrophic factorTrkB rescue of neuroblastoma cells from chemotherapy-induced cell death. Cancer Res.

Li (2005)

. Inhibition of insulin-like growth factor I receptor expression in neuroblastoma cells induces the regression of established tumors in mice. Cancer Res.

Liu (1998)

. Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor. Cancer Res.

Ho (2005)

. Increased sensitivity to the platelet-derived growth factor (PDGF) receptor inhibitor STI571 in chemoresistant glioma cells is associated with enhanced PDGF-BB-mediated signaling and STI571-induced Akt inactivation. J Cell Physiol.

Servidei (2006)

PI3King on MYCN to improve neuroblastoma therapeutics. Cancer Cell.

Hogarty (2012)

. Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res.

Chesler (2006)

. Paracrine signaling through MYCN enhances tumor-vascular interactions in neuroblastoma. Sci Transl Med.

Chanthery (2012)

. Stabilization of N-Myc is a critical function of aurora A in human neuroblastoma. Cancer Cell.

Otto (2009)

Insulin-like growth factor-I signaling in human neuroblastoma cells. Oncogene.

Kim (2004)

. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res.

Maloney (2003)

. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer.

Kolb (2008)

. Novel agents targeting the IGF-1RPI3K pathway impair cell proliferation and survival in subsets of medulloblastoma and neuroblastoma. PLoS One.

Wojtalla (2012)

. Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition. Int J Cancer.

Guerreiro (2006)

. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res.

Tanno (2006)

. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Childrens Oncology Group phase 1 consortium study. Lancet Oncol.

Mosse (2013)

. Molecular rationale for the use of PI3KAKTmTOR pathway inhibitors in combination with crizotinib in ALK-mutated neuroblastoma. Oncotarget.

Moore (2014)

. Identification of NVP-BKM120 as a potent, selective, orally bioavailable class I PI3 kinase inhibitor for treating cancer. ACS Med Chem Lett.

Burger (2011)

. A dual PI3 kinasemTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell.

Fan (2006)

. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinasemammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther.

Maira (2008)

. Sequential dosing in chemosensitization: targeting the PI3KAktmTOR pathway in neuroblastoma. PLoS One.

Westhoff (2013)

. PI3K inhibitors prime neuroblastoma cells for chemotherapy by shifting the balance towards pro-apoptotic Bcl-2 proteins and enhanced mitochondrial apoptosis. Oncogene.

Bender (2011)

. Effects of small molecule inhibitors of PI3KAktmTOR signaling on neuroblastoma growth in vitro and in vivo. Int J Cancer.

Segerstrom (2011)

. Targeting aberrant PI3KAkt activation by PI103 restores sensitivity to TRAIL-induced apoptosis in neuroblastoma. Clin Cancer Res.

Opel (2011)

. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol.

Rodon (2013)

. Comprehensive preclinical testing for neuroblastoma using orthotopic xenografts of a patient tumor. J Clin Oncol.

Federico (2012)

. In vitro and in vivo inhibition of neuroblastoma tumor cell growth by AKT inhibitor perifosine. J Natl Cancer Inst.

Li (2010)

Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med.

Seto (2012)

. Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer.

Houghton (2008)

Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors. Mol Cancer Ther.

Kurmasheva (2007)

. Phase I study of everolimus in pediatric patients with refractory solid tumors. J Clin Oncol.

Fouladi (2007)

. A phase I trial to determine the safety, tolerability, and maximum tolerated dose of deforolimus in patients with advanced malignancies. Clin Cancer Res.

Hartford (2009)

. Phase I study of temsirolimus in pediatric patients with recurrentrefractory solid tumors. J Clin Oncol.

Spunt (2011)

. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer.

Geoerger (2012)

. Targeting PI3KAKTmTOR pathway in non small cell lung cancer. Biochem Pharmacol.

Fumarola (2014)

. mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling. Apoptosis.

Zhang (2015)

. Emergence of new ALK mutations at relapse of neuroblastoma. J Clin Oncol.

Schleiermacher (2014)

Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging

Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works

Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy

Tewari, D., Patni, P., Bishayee, A., Sah, A. N., & Bishayee, A. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.12.008 · Cited by 655 · see citing works

The role of TGF-β/SMAD4 signaling in cancer

Zhao, M., Mishra, L., & Deng, C.-X. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.23230 · Cited by 631 · see citing works

Epithelial-mesenchymal transition in tissue repair and fibrosis

Stone, R. C., Pastar, I., Ojeh, N. O., Chen, V., Liu, S., Garzon, K. I., & Tomic‐Canic, M. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2464-0 · Cited by 577 · see citing works

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

Xie, Y., Shi, X., Sheng, K., Han, G., Li, W., Zhao, Q., Jiang, B., Feng, J., Li, J., & Gu, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9713 · Cited by 505 · see citing works

Cell-cell communication: New insights and clinical implications

Su, J., Song, Y., Zhu, Z., Huang, X., Fan, J., Qiao, J., & Mao, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01888-z · Cited by 433 · see citing works

Molecular targeting therapies for neuroblastoma: Progress and challenges

Zafar, A., Wang, W., Liu, G., Wang, X., Xian, W., McKeon, F., Foster, J. H., Zhou, J., & Zhang, R. (2020) · Medicinal Research Reviews · doi:10.1002/med.21750 · Cited by 383 · see citing works

Dual or multi-targeting inhibitors: The next generation anticancer agents

Raghavendra, N. M., Pingili, D., Kadasi, S., Mettu, A., & Prasad, S. V. U. M. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.021 · Cited by 333 · see citing works

Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation

Sadiq, I. Z. (2021) · Current Molecular Medicine · doi:10.2174/1566524022666211222161637 · Cited by 284 · see citing works

Molecular Mechanisms of Action of FSH

Casarini, L., & Crépieux, P. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00305 · Cited by 265 · see citing works

The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds

Roy, T., Boateng, S. T., Uddin, M. B., Banang‐Mbeumi, S., Yadav, R. K., Bock, C. R., Folahan, J. T., Siwe‐Noundou, X., Walker, A. L., King, J. A. C., et al. (2023) · Cells · doi:10.3390/cells12121671 · Cited by 173 · see citing works

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Zhang, L., Li, Y., Wang, Q., Chen, Z., Li, X., Wu, Z., Hu, C., Liao, D., Zhang, W., & Chen, Z.-S. (2020) · Molecular Cancer · doi:10.1186/s12943-019-1112-1 · Cited by 152 · see citing works

Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review

Tang, Y., Wang, D., Wang, Y., Huang, A., & Xu, W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1073971 · Cited by 126 · see citing works

Neuroblastoma treatment in the post-genomic era

Esposito, M. R., Aveic, S., Seydel, A., & Tonini, G. P. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0319-y · Cited by 113 · see citing works

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun, X., Yan, P., Zou, C., Wong, Y., Shu, Y., Lee, Y. M., Zhang, C., Yang, N., Wang, J., & Zhang, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21580 · Cited by 113 · see citing works

The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review

Shamsan, E., Almezgagi, M., Gamah, M., Khan, N., Qasem, A., Chuanchuan, L., & Haining, F. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1389329 · Cited by 113 · see citing works

Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells

Lin, X., Han, L., Weng, J., Wang, K., & Chen, T. (2018) · Bioscience Reports · doi:10.1042/bsr20181822 · Cited by 110 · see citing works

Dysregulation of PI3K-Akt-mTOR pathway in brain of streptozotocin-induced type 2 diabetes mellitus in Wistar rats

Bathina, S., & Das, U. N. (2018) · Lipids in Health and Disease · doi:10.1186/s12944-018-0809-2 · Cited by 103 · see citing works

Targeting PI3K/Akt signaling in prostate cancer therapy

Hashemi, M., Taheriazam, A., Daneii, P., Hassanpour, A., Kakavand, A., Rezaei, S., Hejazi, E. S., Aboutalebi, M., Gholamrezaie, H., Saebfar, H., et al. (2022) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-022-00702-1 · Cited by 100 · see citing works

Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials

Simile, M. M., Bagella, P., Vidili, G., et al. (2019) · Medicina · doi:10.3390/medicina55020042 · Cited by 95 · see citing works

Polo-like kinase 4 mediates epithelial–mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway

Tian, X., Zhou, D., Chen, L., Tian, Y., Zhong, B., Cao, Y., Dong, Q., Zhou, M., Yan, J. Y., Wang, Y., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0088-2 · Cited by 93 · see citing works

The emerging role of non-coding RNAs in the regulation of PI3K/AKT pathway in the carcinogenesis process

Ghafouri‐Fard, S., Abak, A., Anamag, F. T., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111279 · Cited by 76 · see citing works

A review of the biological and clinical implications of RAS-MAPK pathway alterations in neuroblastoma

Mlakar, V., Morel, E., Mlakar, S. J., Ansari, M., & Gumy‐Pause, F. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01967-x · Cited by 69 · see citing works

Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway

Wang, S., Wang, C., Chang, L.-M., Zhou, K., Wang, J.-W., Ke, Y., Yang, D., Shi, H., Wang, R., Shi, X., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12166 · Cited by 67 · see citing works

Discovery and repurposing of artemisinin

Shi, Q., Xia, F., Wang, Q., Liao, F., Guo, Q., Xu, C., & Wang, J. (2022) · Frontiers of Medicine · doi:10.1007/s11684-021-0898-6 · Cited by 67 · see citing works

Apoptosis induced by the methanol extract of Salvia miltiorrhiza Bunge in non-small cell lung cancer through PTEN-mediated inhibition of PI3K/Akt pathway

Ye, Y., Zhong, W., Sun, P., et al. (2017) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.12.051 · Cited by 67 · see citing works

mir‑106a regulates cell proliferation and apoptosis of colon cancer cells through targeting the PTEN/PI3K/AKT signaling pathway

Qin, Y., Huo, Z., Song, X., Chen, X., Tian, X., & Wang, X.-J. (2017) · Oncology Letters · doi:10.3892/ol.2017.7715 · Cited by 65 · see citing works

Phytochemicals and PI3K Inhibitors in Cancer—An Insight

Suvarna, V., Murahari, M., Khan, T. A., Chaubey, P., & Sangave, P. C. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00916 · Cited by 64 · see citing works

Exploration of therapeutic applicability and different signaling mechanism of various phytopharmacological agents for treatment of breast cancer

Singh, V., Kumar, K., Purohit, D., Verma, R., Pandey, P., Bhatia, S., Malik, V., Mittal, V., Rahman, M. H., Albadrani, G. M., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111584 · Cited by 61 · see citing works

The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis

Snapkov, I., Öqvist, C. O., Figenschau, Y., et al. (2016) · BMC Cancer · doi:10.1186/s12885-016-2545-1 · Cited by 61 · see citing works

Butylated Hydroxyanisole Exerts Neurotoxic Effects by Promoting Cytosolic Calcium Accumulation and Endoplasmic Reticulum Stress in Astrocytes

Park, S., Lee, J., Lim, W., You, S., & Song, G. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b02899 · Cited by 58 · see citing works

The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma

Bahmad, H. F., Mouhieddine, T. H., Chalhoub, R., Assi, S., Araji, T., Chamaa, F., Itani, M. M., Nokkari, A., Kobeissy, F. H., Daoud, G., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.26088 · Cited by 54 · see citing works

Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways

Subramonian, D., Phanhthilath, N., Rinehardt, H., Flynn, S. M., Huo, Y., Zhang, J., Messer, K. S., Mo, Q., Huang, S., Lesperance, J., et al. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0905-8 · Cited by 53 · see citing works

Recent advances with 5‐HT3 modulators for neuropsychiatric and gastrointestinal disorders

Jůza, R., Vlček, P., Mezeiová, E., Musílek, K., Soukup, O., & Korábečný, J. (2020) · Medicinal Research Reviews · doi:10.1002/med.21666 · Cited by 52 · see citing works

Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect

Kim, S., & Baek, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126173 · Cited by 54 · see citing works

The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status

Dumbuya, J. S., Chen, L., Wu, J., & Bin, W. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02084-4 · Cited by 51 · see citing works

Anti-cancer and Sensibilisation Effect of Triptolide on Human Epithelial Ovarian Cancer

Hu, H., Luo, L., Liu, F., Zou, D., Zhu, S., Tan, B., & Chen, T. (2016) · Journal of Cancer · doi:10.7150/jca.16178 · Cited by 49 · see citing works

Differential Binding of Three Major Human ADAR Isoforms to Coding and Long Non-Coding Transcripts

Galipon, J., Ishii, R., Suzuki, Y., et al. (2017) · Genes · doi:10.3390/genes8020068 · Cited by 49 · see citing works

Hypericin inhibits hepatitis C virus replication via deacetylation and down-regulation of heme oxygenase-1

Chao-Ming, S., Wu, C., Wu, W., et al. (2017) · Phytomedicine · doi:10.1016/j.phymed.2017.08.009 · Cited by 49 · see citing works

Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway

Liu, X., Tan, X., Liu, P., Wu, Y., Qian, S., & Zhang, X. (2018) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504018x15166223632406 · Cited by 49 · see citing works

Epigenetic Regulation of Cancer Stem Cells by the Aryl Hydrocarbon Receptor Pathway

Akhtar, S., Hourani, S., Therachiyil, L., Al‐Dhfyan, A., Agouni, A., Zeidan, A., Shahab Uddin, M. S., & Korashy, H. M. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.08.014 · Cited by 49 · see citing works

Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo

Tümmler, C., Snapkov, I., Wickström, M., Moens, U. L., Ljungblad, L. M., Elfman, L. H. M., Winberg, J., Kogner, P., Johnsen, J. I., & Sveinbjørnsson, B. (2017) · Oncotarget · doi:10.18632/oncotarget.19619 · Cited by 48 · see citing works

6-Aryl substituted 4-(4-cyanomethyl) phenylamino quinazolines as a new class of isoform-selective PI3K-alpha inhibitors

Yadav, R. R., Guru, S. K., Joshi, P., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.07.006 · Cited by 47 · see citing works

The Long and the Short of PTEN in the Regulation of Mitophagy

Wang, L., Lu, G. X., & Shen, H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00299 · Cited by 45 · see citing works

Suppression of STIM1 inhibits the migration and invasion of human prostate cancer cells and is associated with PI3K/Akt signaling inactivation

Zhou, Y., Gu, P., Li, J., Li, F., Zhu, J., Gao, P., Zang, Y., Wang, Y., Shan, Y., & Yang, D. (2017) · Oncology Reports · doi:10.3892/or.2017.5961 · Cited by 45 · see citing works

MiR-17 targets PTEN and facilitates glial scar formation after spinal cord injuries via the PI3K/Akt/mTOR pathway

Luan, Y., Chen, M., & Zhou, L. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.09.017 · Cited by 44 · see citing works

Sex Hormones and Inflammation Role in Oral Cancer Progression: A Molecular and Biological Point of View

Contaldo, M., Boccellino, M., Zannini, G., Romano, A., Sciarra, A., Sacco, A., Settembre, G., Coppola, M., Carlo, A. D., D’Angelo, L., et al. (2020) · Journal of Oncology · doi:10.1155/2020/9587971 · Cited by 42 · see citing works

Sarcopenic Obesity: Involvement of Oxidative Stress and Beneficial Role of Antioxidant Flavonoids

Jung, U. J. (2023) · Antioxidants · doi:10.3390/antiox12051063 · Cited by 41 · see citing works

Insulin regulates titin pre-mRNA splicing through the PI3K-Akt-mTOR kinase axis in a RBM20-dependent manner

Zhu, C., Yin, Z., Tan, B., & Guo, W. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.023 · Cited by 38 · see citing works

PI3K-AKT-GSK3β-CREB signaling pathway regulates anxiety-like behavior in rats following alcohol withdrawal

Qiao, X., Gai, H., Su, R., Deji, C., Cui, J., Lai, J., & Zhu, Y. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.04.039 · Cited by 41 · see citing works

The role of hypoxic microenvironment in autoimmune diseases

Gong, X., Yang, S.-Y., Wang, Z.-Y., & Tang, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1435306 · Cited by 40 · see citing works

PI3K/AKT/p53 pathway inhibits infectious spleen and kidney necrosis virus infection by regulating autophagy and immune responses

Zhang, X., Ming, Y., Fu, X., Niu, Y., Lin, Q., Liang, H., Luo, X., Liu, L., & Li, N. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.12.046 · Cited by 37 · see citing works

Icaritin: A Novel Natural Candidate for Hematological Malignancies Therapy

Yang, X., Xi, Y.-M., & Li, Z. (2019) · BioMed Research International · doi:10.1155/2019/4860268 · Cited by 38 · see citing works

Crosstalk between PI3K/AKT/KLF4 signaling and microglia M1/M2 polarization as a novel mechanistic approach towards flibanserin repositioning in parkinson's disease

El-Deeb, N. K., El-Tanbouly, D. M., Khattab, M. A., El-Yamany, M. F., & Mohamed, A. F. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109191 · Cited by 39 · see citing works

Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting

Qiang, M., Chen, Z., Liu, H., Dong, J., Gong, K., Zhang, X., Huo, P., Zhu, J., Shao, Y., Ma, J., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1516583 · Cited by 45 · see citing works

Implication of the PI3K/Akt/mTOR Pathway in the Process of Incompetent Valves in Patients with Chronic Venous Insufficiency and the Relationship with Aging

Ortega, M. A., Asúnsolo, Á., Leal, J., Romero, B., Álvarez-Rocha, M. J., Sáinz, F., Álvarez‐Mon, M., Buján, J., & García‐Honduvilla, N. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1495170 · Cited by 35 · see citing works

Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques

Natunen, T., Martiskainen, H., Marttinen, M., Gabbouj, S., Koivisto, H., Kemppainen, S., Kaipainen, S., Takalo, M., Svobodová, H., Leppänen, L., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00415-2 · Cited by 34 · see citing works

Antioxidant and Anti-inflammatory Effects of Marine Phlorotannins and Bromophenols Supportive of Their Anticancer Potential

Goya, L., & Mateos, R. (2024) · Nutrition Reviews · doi:10.1093/nutrit/nuae066 · Cited by 33 · see citing works

Identification of The Aberrantly Expressed LncRNAs in Hepatocellular Carcinoma: A Bioinformatics Analysis Based on RNA-sequencing

Liao, H., Huang, J., Lan, T., Wang, J., Zhu, B., Yuan, K., & Zeng, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-23647-1 · Cited by 32 · see citing works

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

Moody, T. W., Lee, L., Ramos-Álvarez, I., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.728088 · Cited by 32 · see citing works

Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol

Gonçalves, M., Aiello, A., Rodríguez-Pérez, M., Accardi, G., Burgos‐Ramos, E., & Silva, P. (2024) · Nutrients · doi:10.3390/nu16060818 · Cited by 31 · see citing works

Cytochrome c and cancer cell metabolism: A new perspective

Alshehri, B. (2024) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2024.102194 · Cited by 32 · see citing works

Nicotine promotes the development of non-small cell lung cancer through activating LINC00460 and PI3K/Akt signaling

Zhao, H., Wang, Y., & Ren, X. (2019) · Bioscience Reports · doi:10.1042/bsr20182443 · Cited by 31 · see citing works

Active Compounds Derived from Fuzheng Huayu Formula Protect Hepatic Parenchymal Cells from Apoptosis Based on Network Pharmacology and Transcriptomic Analysis

Wu, R., Dong, S., Cai, F., et al. (2019) · Molecules · doi:10.3390/molecules24020338 · Cited by 30 · see citing works

Artesunate inhibits proliferation, migration, and invasion of thyroid cancer cells by regulating the PI3K/AKT/FKHR pathway

Xu, Z., Liu, X., & Zhuang, D. (2021) · Biochemistry and Cell Biology · doi:10.1139/bcb-2021-0275 · Cited by 30 · see citing works

Silicosis: from pathogenesis to therapeutics

Bi-jun, Y., Liu, X., Peng, C., Meng, X., & Jia, Q. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1516200 · Cited by 32 · see citing works

Targeting P-selectin blocks neuroblastoma growth

Nolo, R. M., Herbrich, S. M., Rao, A. U. K., Zweidler‐McKay, P. A., Kannan, S., & Gopalakrishnan, V. (2017) · Oncotarget · doi:10.18632/oncotarget.21364 · Cited by 29 · see citing works

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

Soleimani, A., Rahmani, F., Ferns, G. A., Ryzhikov, M., Avan, A., & Hassanian, S. M. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190110151957 · Cited by 29 · see citing works

Inhibition of AKT enhances the anti-cancer effects of Artemisinin in clear cell renal cell carcinoma

Yu, C., Sun, P., Zhou, Y., et al. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109383 · Cited by 29 · see citing works

Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/β-Catenin Pathway Stimulation by Regulating GSK3b Activity

Kim, J. J., Shin, J. Y., Choi, Y.-H., Lee, S. Y., Jin, M. H., Kim, C. D., Kang, N. G., & Lee, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115571 · Cited by 29 · see citing works

Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis

Juźwik, C. A., Drake, S. S., Lécuyer, M.-A., Johnson, R. M., Morquette, B., Zhang, Y., Charabati, M., Sagan, S., Bar-Or, A., Prat, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31542-y · Cited by 29 · see citing works

Combining thioridazine and loratadine for the treatment of gastrointestinal tumor

Chen, T., Hu, Y., Liu, B., et al. (2017) · Oncology Letters · doi:10.3892/ol.2017.6815 · Cited by 28 · see citing works

Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo

Xu, D., Toyoda, H., Yuan, X., et al. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.02.032 · Cited by 28 · see citing works

Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma

Ruckert, M. T., de Andrade, P. V., Santos, V. S., & Silveira, V. S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03095-4 · Cited by 27 · see citing works

Characterization of the in vitro cytotoxic effects of brachydins isolated from Fridericia platyphylla in a prostate cancer cell line

Nunes, H. L., Tuttis, K., Serpeloni, J. M., et al. (2020) · Journal of Toxicology and Environmental Health · doi:10.1080/15287394.2020.1784339 · Cited by 27 · see citing works

MicroRNAs as the critical regulators of tyrosine kinase inhibitors resistance in lung tumor cells

Maharati, A., Zangouei, A. S., Khalili‐Tanha, G., & Moghbeli, M. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00840-4 · Cited by 27 · see citing works

A sketch of known and novel MYCN-associated miRNA networks in neuroblastoma

Megiorni, F., Colaiacovo, M., Cialfi, S., McDowell, H. P., Guffanti, A., Camero, S., Felsani, A., Losty, P. D., Pizer, B. L., Shukla, R., et al. (2017) · Oncology Reports · doi:10.3892/or.2017.5701 · Cited by 25 · see citing works

The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma

Lampis, S., Raieli, S., Montemurro, L., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02367-5 · Cited by 26 · see citing works

TOFA induces cell cycle arrest and apoptosis in ACHN and 786-O cells through inhibiting PI3K/Akt/mTOR pathway

He, D., Sun, X., Yang, H., et al. (2018) · Journal of Cancer · doi:10.7150/jca.26374 · Cited by 26 · see citing works

PI3K activation within ventromedial prefrontal cortex regulates the expression of drug‐seeking in two rodent species

Szumlinski, K. K., Ary, A. W., Shin, C., Wroten, M. G., Courson, J. A., Miller, B. W., Ruppert‐Majer, M. A., Hiller, J. W., Shahin, J. R., Ben‐Shahar, O., et al. (2018) · Addiction Biology · doi:10.1111/adb.12696 · Cited by 25 · see citing works

Response of the PI3K‐AKT signalling pathway to low salinity and the effect of its inhibition mediated by wortmannin on ion channels in turbot Scophthalmus maximus

Cui, W., Ma, A., & Wang, X. (2020) · Aquaculture Research · doi:10.1111/are.14607 · Cited by 25 · see citing works

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses

Fang, Y., Ma, M., Wang, J., Liu, X., & Wang, Y. (2017) · Tumor Biology · doi:10.1177/1010428317705850 · Cited by 25 · see citing works

Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research

Sharma, R., Yadav, J., Bhat, S. A., Musayev, A., Myrzagulova, S., Sharma, D., Padha, N., Saini, M., Tuli, H. S., & Singh, T. (2025) · Molecular Neurobiology · doi:10.1007/s12035-024-04680-w · Cited by 29 · see citing works

Piperine loaded zinc oxide nanocomposite inhibits the PI3K/AKT/mTOR signaling pathway via attenuating the development of gastric carcinoma: In vitroandin vivostudies

Yang, Z., Pu, M., Dong, X., Ji, F., Veeraraghavan, V. P., & Yang, H. (2020) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2020.03.028 · Cited by 24 · see citing works

HnRNP-F promotes the proliferation of bladder cancer cells mediated by PI3K/AKT/FOXO1

Li, F., Xie, W., Fang, Y., Xie, K., Liu, W., Hou, L., & Tan, W. (2020) · Journal of Cancer · doi:10.7150/jca.50490 · Cited by 24 · see citing works

Current biomarker-associated procedures of cancer modeling-a reference in the context of IDH1 mutant glioma

Mehrjardi, N. Z., Hänggi, D., & Kahlert, U. D. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03196-0 · Cited by 23 · see citing works

Silencing of epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1)viasiRNA-induced cell death in glioblastoma

Serban, F., Daianu, O., Tătăranu, L. G., Artene, Ş.-A., Emami, G., Georgescu, A. M., Alexandru, O., Purcaru, Ş. O., Tache, D. E., Dănciulescu, M. M., et al. (2016) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2016.1209217 · Cited by 24 · see citing works

Dysbindin promotes progression of pancreatic ductal adenocarcinoma via direct activation of PI3K

Fang, C., Guo, X., Lv, X., et al. (2017) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjx043 · Cited by 24 · see citing works

Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord

Ren, Z., Wang, X., Xu, M., Frank, J. A., & Luo, J. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.12.002 · Cited by 24 · see citing works

Triptolide sensitizes cisplatin-resistant human epithelial ovarian cancer by inhibiting the phosphorylation of AKT

Huang, G., Hu, H., Zhang, Y., Zhu, Y., Liu, J., Tan, B., & Chen, T. (2019) · Journal of Cancer · doi:10.7150/jca.30669 · Cited by 23 · see citing works

Harnessing the role of aberrant cell signaling pathways in glioblastoma multiforme: a prospect towards the targeted therapy

Hasan, S., Mahmud, Z., Hossain, M., & Islam, S. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09996-3 · Cited by 23 · see citing works

Neurotoxicity of local anesthetics in dentistry

Kim, E.-J., Kim, H. Y., & Ahn, J.-H. (2020) · Journal of Dental Anesthesia and Pain Medicine · doi:10.17245/jdapm.2020.20.2.55 · Cited by 23 · see citing works

Association of a genetic variant in AKT1 gene with features of the metabolic syndrome

Eshaghi, F. S., Ghazizadeh, H., Kazami-Nooreini, S., Timar, A., Esmaeily, H., Mehramiz, M., Avan, A., & Ghayour‐Mobarhan, M. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.03.002 · Cited by 23 · see citing works

Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells

Waetzig, R., Matthes, M., Leister, J., Penkivech, G., Heise, T., Corbacioglu, S., & Sommer, G. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.48393 · Cited by 23 · see citing works

Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme

Mazurek, M., Grochowski, C., Litak, J., Osuchowska, I., Maciejewski, R., & Kamieniak, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093046 · Cited by 22 · see citing works

Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/β-Catenin Pathway Stimulation via Modulation of Gsk3β Activity in Cultured Human Dermal Papilla Cells

Kim, J. J., Shin, J. Y., Choi, Y.-H., Kang, N. G., & Lee, S. (2022) · Molecules · doi:10.3390/molecules27072184 · Cited by 23 · see citing works

Thalidomide attenuates development of morphine dependence in mice by inhibiting PI3K/Akt and nitric oxide signaling pathways

Khan, M. I., Momeny, M., Ostadhadi, S., et al. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.002 · Cited by 22 · see citing works

Solanine Interferes with AKT/p-AKT and PI3K/p-PI3K Pathway to Inhibit HIF and Destroy Cell Energy Metabolism

Wang, Y., Wang, P., & Zhao, W. (2021) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2021.910008 · Cited by 1 · see citing works

Reactivation of AKT signaling following treatment of cancer cells with PI3K inhibitors attenuates their antitumor effects

Dufour, M., Dormond-Meuwly, A., Pythoud, C., Demartines, N., & Dormond, O. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.07.014 · Cited by 21 · see citing works

FoxO Transcription Factors Promote AKT Ser473 Phosphorylation and Renal Tumor Growth in Response to Pharmacologic Inhibition of the PI3K–AKT Pathway

Lin, A., Piao, H.-L., Li, Z., Sarbassov, D. D., Ma, L., & Gan, B. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1729 · Cited by 148 · see citing works

Virtual Docking Screening and QSAR Studies to Explore PI3K and mTOR Inhibitors Acting on AKT in Cancers

Kandoussi, I., Benherrif, O., Lakhlili, W., et al. (2020) · Journal of Cancer Science and Clinical Therapeutics · doi:10.26502/jcsct.5079099 · Cited by 1 · see citing works

Solanine Interferes With AKT/p-AKT and PI3K/ p-PI3K to Inhibit HIF and Destroy Cell Energy MetabolismPreprint

Wang, P., & Wang, Y. (2021) · Research Square · doi:10.21203/rs.3.rs-663150/v1