Targeting PI3K signalling in cancer: opportunities, challenges and limitations

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

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Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

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EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

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Comprehensive genomic characterization defines human glioblastoma genes and core pathways

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Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

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The phosphoinositide 3-kinase pathway

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PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

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MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

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New inhibitors of the mammalian target of rapamycin signaling pathway for cancer

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Tirucallic Acids Are Novel Pleckstrin Homology Domain-Dependent Akt Inhibitors Inducing Apoptosis in Prostate Cancer Cells

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Investigational drug MLN0128, a novel TORC1/2 inhibitor, demonstrates potent oral antitumor activity in human breast cancer xenograft models

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Genotype-Dependent Efficacy of a Dual PI3K/mTOR Inhibitor, NVP-BEZ235, and an mTOR Inhibitor, RAD001, in Endometrial Carcinomas

Shoji, K., Oda, K., Kashiyama, T., Ikeda, Y., Nakagawa, S., Sone, K., Miyamoto, Y., Hiraike, H., Tanikawa, M., Miyasaka, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037431 · Cited by 78

Runx2 activates PI3K/Akt signaling via mTORC2 regulation in invasive breast cancer cells

Tandon, M., Chen, Z., & Pratap, J. (2014) · Breast Cancer Research · doi:10.1186/bcr3611 · Cited by 78

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

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The Crucial Role of Inflammation and the Immune System in Colorectal Cancer Carcinogenesis: A Comprehensive Perspective

Burgos-Molina, A. M., Santana, T. T., Redondo, M., & Romero, M. J. B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116188 · Cited by 87

A Novel Oncolytic Herpes Simplex Virus that Synergizes with Phosphoinositide 3-kinase/Akt Pathway Inhibitors to Target Glioblastoma Stem Cells

Kanai, R., Wakimoto, H., Martuza, R. L., & Rabkin, S. D. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3142 · Cited by 78

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

Al-Shamsi, H. O., Jones, J. C., Fahmawi, Y., Dahbour, I., Tabash, A., Abdel‐Wahab, R., Abousamra, A., Shaw, K. R. M., Xiao, L., Hassan, M. M., et al. (2016) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2016.11.02 · Cited by 79

Buparlisib is a brain penetrable pan-PI3K inhibitor

de Gooijer, M. C., Zhang, P., Buil, L. C. M., Çitirikkaya, C. H., Thota, N., Beijnen, J. H., & van Tellingen, O. (2018) · Scientific Reports · doi:10.1038/s41598-018-29062-w · Cited by 80

Beyond chemotherapy: new agents for targeted treatment of lymphoma

Younes, A. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.189 · Cited by 78

Synthetic lethal interaction between PI3K/Akt/mTOR and Ras/MEK/ERK pathway inhibition in rhabdomyosarcoma

Guenther, M. K., Graab, U., & Fulda, S. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.05.010 · Cited by 79

Integrating synthetic accessibility with AI-based generative drug design

Parrot, M., Tajmouati, H., da Silva, V. B. R., Atwood, B. R., Fourcade, R., Gaston‐Mathé, Y., Huu, N. D., & Perron, Q. (2023) · Journal of Cheminformatics · doi:10.1186/s13321-023-00742-8 · Cited by 85

The diverse role of the PPARγ coactivator 1 family of transcriptional coactivators in cancer

Girnun, G. D. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.01.007 · Cited by 76

Thymoquinone induces G2/M arrest, inactivates PI3K/Akt and nuclear factor-κB pathways in human cholangiocarcinomas both in vitro and in vivo

Xu, D., Ma, Y., Zhao, B., LI, S., Zhang, Y., Pan, S., Wu, Y., Wang, J., Wang, D., Pan, H., et al. (2014) · Oncology Reports · doi:10.3892/or.2014.3059 · Cited by 77

The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase

Erazo, T., Lorente, M., López‐Plana, A., Muñoz‐Guardiola, P., Fernández‐Nogueira, P., García-Martínez, J. A., Bragado, P., Fuster, G., Salazar‐Roa, M., Espadaler, J., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1808 · Cited by 81

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A

Choi, S. K., Kim, H., Jin, T.-F., Hwang, E. H., Jung, M., & Moon, W. (2016) · BMC Cancer · doi:10.1186/s12885-016-2620-7 · Cited by 74

Fibrinogen promotes malignant biological tumor behavior involving epithelial–mesenchymal transition via the p-AKT/p-mTOR pathway in esophageal squamous cell carcinoma

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Therapeutic potential of targeting SHP2 in human developmental disorders and cancers

Shen, D., Chen, W., Zhu, J., Wu, G., Shen, R., Xi, M., & Sun, H. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112117 · Cited by 79

Smarter drugs emerging in pancreatic cancer therapy

Kleger, A., Perkhofer, L., & Seufferlein, T. T. W. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu013 · Cited by 78

Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities

Roy, D., Sheng, G. Y., Semukunzi, H., de Carvalho, E. L., Mahanty, A., Yuan, S., & Sun, L. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.01.019 · Cited by 76

Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor

Fan, Y., Xue, W., Schachner, M., & Zhao, W. (2018) · Cancers · doi:10.3390/cancers11010022 · Cited by 76

Cancer immunotherapy with PI3K and PD-1 dual-blockade via optimal modulation of T cell activation signal

Isoyama, S., Mori, S., Sugiyama, D., Kojima, Y., Tada, Y., Shitara, K., Hinohara, K., Dan, S., & Nishikawa, H. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002279 · Cited by 76

Oridonin: targeting programmed cell death pathways as an anti‐tumour agent

Liu, Z.-Y., Ouyang, L., Peng, H. F., & Zhang, W. (2012) · Cell Proliferation · doi:10.1111/j.1365-2184.2012.00849.x · Cited by 75

Genomic Profiling of Advanced-Stage, Metaplastic Breast Carcinoma by Next-Generation Sequencing Reveals Frequent, Targetable Genomic Abnormalities and Potential New Treatment Options

Ross, J. S., Badve, S., Wang, K., Sheehan, C. E., Boguniewicz, A. B., Otto, G. A., Yelensky, R., Lipson, D., Ali, S. M., Morosini, D., et al. (2015) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2014-0200-oa · Cited by 77

Role of Akt signaling in resistance to DNA-targeted therapy

Avan, A., Narayan, R. S., Giovannetti, E., & Peters, G. J. (2016) · World Journal of Clinical Oncology · doi:10.5306/wjco.v7.i5.352 · Cited by 77

Role of Aspirin in Breast Cancer Survival

Chen, W. Y., & Holmes, M. D. (2017) · Current Oncology Reports · doi:10.1007/s11912-017-0605-6 · Cited by 76

LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma

Vieira, G. C., Chockalingam, S., Melegh, Z., Greenhough, A., Malik, S., Szemes, M., Park, J. H., Kaidi, A., Zhou, L., Catchpoole, D. R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5548 · Cited by 75

Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines

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Suppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway

Li, B., Li, J., Xu, W., Guan, X., Qin, Y.-R., Zhang, L. Y., Law, S. Y.-K., Tsao, S. W., & Cheung, A. L. M. (2014) · Oncotarget · doi:10.18632/oncotarget.2596 · Cited by 76

Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways

Tiong, Y. L., Ng, K. Y., Koh, R. Y., Ponnudurai, G., & Chye, S. M. (2019) · Antioxidants · doi:10.3390/antiox8070198 · Cited by 79

Autophagy regulation in cancer development and therapy.

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Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells

Wang, Y., Sheng, Q., Spillman, M. A., Behbakht, K., & Gu, H. (2011) · Oncogene · doi:10.1038/onc.2011.435 · Cited by 75

Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies

Bowles, D. W., Diamond, J. R., Lam, E. T., Weekes, C. D., Astling, D. P., Anderson, R. T., Leong, S., Gore, L., Varella‐Garcia, M., Vogler, B. W., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2506 · Cited by 75

Extracellular Matrix Regulation of Metabolism and Implications for TumorigenesisPreprint

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PTEN deficiency is associated with reduced sensitivity to mTOR inhibitor in human bladder cancer through the unhampered feedback loop driving PI3K/Akt activation

Seront, E., Pinto, A., Bouzin, C., Bertrand, L., Jp, M., & Féron, O. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.505 · Cited by 75

In Vivo Activity of Combined PI3K/mTOR and MEK Inhibition in a KrasG12D ; Pten Deletion Mouse Model of Ovarian Cancer

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Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

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Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways

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Allosteric and ATP-competitive kinase inhibitors of mTOR for cancer treatment

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VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the Treatment of Cancer

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α5β1-Integrin promotes tension-dependent mammary epithelial cell invasion by engaging the fibronectin synergy site

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The role of mitogen‐ and stress‐activated protein kinase pathways in melanoma

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MicroRNA-374b Suppresses Proliferation and Promotes Apoptosis in T-cell Lymphoblastic Lymphoma by Repressing AKT1 and Wnt-16

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Intracellular Protein Delivery and Gene Transfection by Electroporation Using a Microneedle Electrode Array

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The PIM kinases in hematological cancers

Alvarado, Y., Giles, F. J., & Swords, R. T. (2012) · Expert Review of Hematology · doi:10.1586/ehm.11.69 · Cited by 75

Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway

Soo, H. C., Chung, F. F., Lim, K., Yap, V. A., Bradshaw, T. D., Hii, L., Tan, S.-H., See, S.-J., Tan, Y.-F., Leong, C., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170551 · Cited by 73

Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival

Werfel, T. A., Wang, S., Jackson, M. A., Kavanaugh, T. E., Joly, M. M., Lee, L., Hicks, D. J., Sanchez, V. M., Ericsson, P. I. G., Kilchrist, K. V., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2388 · Cited by 73

The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting

Jonckheere, N., Vasseur, R., & SEUNINGEN, I. V. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.01.002 · Cited by 73

Recent nanotechnological interventions targeting PI3K/Akt/mTOR pathway: A focus on breast cancer

Sharma, V., Sharma, A. K., Punj, V., & Priya, P. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.005 · Cited by 72

Cancer Biology and Prevention in Diabetes

Srivastava, S. P., & Goodwin, J. E. (2020) · Cells · doi:10.3390/cells9061380 · Cited by 77

Quercitrin alleviates cartilage extracellular matrix degradation and delays ACLT rat osteoarthritis development: An in vivo and in vitro study

Guo, H., Yin, W., Zou, Z., Zhang, C., Sun, M., Min, L., Yang, L., & Kong, L. (2020) · Journal of Advanced Research · doi:10.1016/j.jare.2020.06.020 · Cited by 72

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression

Xia, C., Liu, C., He, Z., Cai, Y., & Chen, J. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01627-6 · Cited by 75

Tumor Heterogeneity Revealed byKRAS,BRAF, andPIK3CAPyrosequencing:KRASandPIK3CAIntratumor Mutation Profile Differences and Their Therapeutic Implications

Kosmidou, V., Oikonomou, E., Vlassi, M., Avlonitis, S., Katseli, A., Tsipras, I., Mourtzoukou, D., Kontogeorgos, G., Zografos, G., & Pintzas, A. (2013) · Human Mutation · doi:10.1002/humu.22496 · Cited by 74

Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination

Jo, H., Lo, P., Li, Y., Loison, F., Green, S., Wang, J. X., Silberstein, L. E., Ye, K., Chen, H., & Luo, H. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019062108 · Cited by 73

Aberrant receptor tyrosine kinase signaling in lipofibromatosis: a clinicopathological and molecular genetic study of 20 cases

Al‐Ibraheemi, A., Folpe, A. L., Pérez‐Atayde, A. R., Perry, K., Hofvander, J., Arbajian, E., Magnusson, L., Nilsson, J., & Mertens, F. (2018) · Modern Pathology · doi:10.1038/s41379-018-0150-3 · Cited by 72

Baicalin alleviates TNBS‑induced colitis by inhibiting PI3K/AKT pathway activation

Zhu, L., Shen, H., Gu, P., Liu, Y., Zhang, L., & Cheng, J. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8718 · Cited by 71

The Role of Periostin in Angiogenesis and Lymphangiogenesis in Tumors

Wasik, A., Ratajczak‐Wielgomas, K., Bądziński, A., Dzięgiel, P., & Podhorska‐Okołów, M. (2022) · Cancers · doi:10.3390/cancers14174225 · Cited by 73

Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Bartucci, M., Svensson, S., Ricci‐Vitiani, L., Dattilo, R., Biffoni, M., Signore, M., Ferla, R., Maria, R. D., & Surmacz, E. (2010) · Endocrine Related Cancer · doi:10.1677/erc-10-0083 · Cited by 71

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Chen, B., Wang, J., Dai, D., Zhou, Q. S., Guo, X., Tian, Z., Huang, X., Yang, L., Tang, H., & Xie, X. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0522-4 · Cited by 71

Antitumor effects of α‐bisabolol against pancreatic cancer

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The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies

Fokas, E., McKenna, W. G., & Muschel, R. J. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9394-4 · Cited by 70

Lipid rafts, KCa/ClCa/Ca2+ channel complexes and EGFR signaling: Novel targets to reduce tumor development by lipids?

Guéguinou, M., Gambade, A., Félix, R., Chantôme, A., Fourbon, Y., Bougnoux, P., Weber, G., Potier‐Cartereau, M., & Vandier, C. (2014) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.10.036 · Cited by 68

Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer

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MicroRNA‐10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway

Hu, R., Pan, W., Fedulov, A. V., Jester, W. F., Jones, M. R., Weiss, S. T., Panettieri, R. A., Tantisira, K. G., & Lu, Q. (2014) · The FASEB Journal · doi:10.1096/fj.13-247247 · Cited by 71

A Potent Combination of the Novel PI3K Inhibitor, GDC-0941, with Imatinib in Gastrointestinal Stromal Tumor Xenografts: Long-Lasting Responses after Treatment Withdrawal

Floris, G., Woźniak, A., Sciot, R., Li, H., Friedman, L. S., Looy, T. V., Wellens, J., Vermaelen, P., Deroose, C. M., Fletcher, J. A., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2853 · Cited by 70

Targeting the PI3K Pathway in the Brain—Efficacy of a PI3K Inhibitor Optimized to Cross the Blood–Brain Barrier

Salphati, L., Heffron, T. P., Alicke, B., Nishimura, M. C., Barck, K. H., Carano, R. A. D., Cheong, J., Edgar, K. A., Greve, J. M., Kharbanda, S., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0720 · Cited by 73

Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors

Sharma, S., Singh, J., Ojha, R., Singh, H., Kaur, M., Bedi, P. M. S., & Nepali, K. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.02.018 · Cited by 70

CXCR1/Akt signaling activation induced by mesenchymal stem cell-derived IL-8 promotes osteosarcoma cell anoikis resistance and pulmonary metastasis

Du, L., Han, X.-G., Tu, B., Wang, M.-Q., Qiao, H., Zhang, S.-H., Fan, Q.-M., & Tang, T.-T. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0745-0 · Cited by 70

The impact of PTEN regulation by CK2 on PI3K-dependent signaling and leukemia cell survival

Barata, J. T. (2010) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2010.09.012 · Cited by 69

Resveratrol Sensitizes Tamoxifen in Antiestrogen-Resistant Breast Cancer Cells with Epithelial-Mesenchymal Transition Features

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Identification of Antrocin from Antrodia camphorata as a Selective and Novel Class of Small Molecule Inhibitor of Akt/mTOR Signaling in Metastatic Breast Cancer MDA-MB-231 Cells

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Antitumor Efficacy of α-Solanine against Pancreatic Cancer In Vitro and In Vivo

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