Cited by 268PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesMetabolism, Diabetes, and Cancer

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mTOR inhibitors in cancer therapy

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Xie, Jianling, Wang, Xuemin, Proud, Christopher G.·2016·F1000Research

DOI 10.12688/f1000research.9207.1PMC PMC5007757

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Abstract

The mammalian target of rapamycin, mTOR, plays key roles in cell growth and proliferation, acting at the catalytic subunit of two protein kinase complexes: mTOR complexes 1 and 2 (mTORC1/2). mTORC1 signaling is switched on by several oncogenic signaling pathways and is accordingly hyperactive in the majority of cancers. Inhibiting mTORC1 signaling has therefore attracted great attention as an anti-cancer therapy. However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology.

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Figure 1. Schematic representation of signaling pathways involving the two mTOR complexes. Typically, hormones and growth factors activate mTOR complex 1 (mTORC1) through the SOS/Ras/Raf-MEK-ERK (MAPK) or the IRS1/PI3K-PDK1-PKB pathways or both. mTORC2 also contributes to the activation of PKB through the direct phosphorylation of its turn motif as well as its hydrophobic motif. These pathways impinge on the tuberous sclerosis complex (TSC), which serves as a GTPase activator protein for the small G-protein Rheb. Upon inhibitory phosphorylation evoked by upstream kinases such as PKB, the activity of TSC is suppressed, promoting the accumulation of GTP-bound Rheb, which in turn activates mTORC1 on the surface of lysosomes. Amino acids also activate mTORC1 by bringing the latter onto lysosomes via the Rag GTPases. S6K-rpS6 and 4EBP1-eIF4E are the best-characterized mTORC1 downstream targets and are responsible for controlling a variety of anabolic effects driven by mTORC1. Dashed lines indicate feedback mechanisms. mTOR, mammalian target of rapamycin; PI3K, phosphoinositide 3-kinase.CC BY · PubMed Central

Figure 2. Domains of the mTOR protein and three generations of mTOR inhibitors. mTOR is composed of 2,549 amino acids which can be divided into several structural domains, including HEAT (for anti-parallel α-helices found in Huntingtin, elongation factor 3, PP2 A and TOR1) repeats and FAT (for FRAP, ATM, TRAP), FRB, kinase, and FATC (for C-terminal FAT) domains. The HEAT repeats, located close to the N-terminus of mTOR, are required for mTOR multimerization. The FRB—FK506 binding protein 12 (FKBP12)–rapamycin binding—domain, as its name implies, is the binding site of mTOR to FKBP12 and rapamycin. FAT, kinase, and FATC domains are conserved within the phosphatidylinositol 3-kinase-related kinases (PIKKs) and are essential for maintaining the activity of PIKKs. The first-generation mTOR inhibitors, including rapamycin itself, bind to FKBP12, which in turn interacts with the FRB domain of mTOR to inhibit mTOR activity. The second-generation mTOR inhibitors are ATP-competitive mTOR inhibitors which act as ATP analogues and compete with ATP for the binding to the kinase domain of mTOR. The newly developed third generation of mTOR inhibitors can potentially overcome the drug resistance of cancer cells bearing mTOR FRB/kinase domain mutation; that is, FRB domain mutations (mTOR A2034V and mTOR F2108L) confer resistance to rapalogs (first generation), and a kinase domain mutation (mTOR M2327I) renders resistance to mTOR-KIs (second generation). mTOR, mammalian target of rapamycin.CC BY · PubMed Central

Figure 3. Selected examples of three generations of mTOR inhibitors and dual PI3K/mTOR inhibitors. Chemical structures were drawn by using the website www.emolecules.com. mTOR, mammalian target of rapamycin; PI3K, phosphoinositide 3-kinase.CC BY · PubMed Central

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Background
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Background
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“For the quantification of protein translation, mice were injected intraperitoneally (IP) with 200 μl of a 10 mM solution of OP-Puro dissolved in PBS as previously described[24].”
Method
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“This pathway has been heavily implicated in many cancer types,(70) and several inhibitors of MTOR are in clinical use, including everolimus, temsirolimus, and zotarolimus, with varying degrees of success.(71,72) PMS2 (PMS1 homolog 2, mismatch repair system endonuclease) interacts with MUT1 to form the MutL-α heterodim…”
Background
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Background
Autophagy and mitochondrial metabolism: insights into their role and therapeutic potential in chronic myeloid leukaemia
Baquero, P., Dawson, A., & Helgason, G. V. (2018) · FEBS Journal · doi:10.1111/febs.14659 · Cited by 18
mTORC1-independent translation control in mammalian cells by methionine adenosyltransferase 2A and S-adenosylmethionine
Alam, M. M., Shima, H., Matsuo, Y., Long, N. C., Matsumoto, M., Ishii, Y., Sato, N., Sugiyama, T., Nobuta, R., Hashimoto, S., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102084 · Cited by 16
Targeted therapy for mTORC1-driven tumours through HDAC inhibition by exploiting innate vulnerability of mTORC1 hyper-activation
Yang, F., Sun, S., Wang, C., Haas, M., Yeo, S. K., & Guan, J. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0839-1 · Cited by 16
The Lysosome in Malignant Melanoma: Biology, Function and Therapeutic Applications
Hsu, C., Lee, K., Chiu, Y., Huang, K.-C., Wang, G., Chen, L.-P., Liao, K., & Lin, C. (2022) · Cells · doi:10.3390/cells11091492 · Cited by 15
Tumour Immunotherapy and Applications of Immunological Products: A Review of Literature
Oli, A. N., Adejumo, S. A., Rowaiye, A. B., Ogidigo, J. O., Hampton‐Marcell, J., & Ibeanu, G. C. (2024) · Journal of Immunology Research · doi:10.1155/2024/8481761 · Cited by 17
“Inhibitors targeting this pathway, such as rapamycin (an mTOR inhibitor), have been explored as potential cancer therapies [46].”
Background
Identification of mTOR inhibitor-resistant genes in cutaneous squamous cell carcinoma
Yu, S., Lee, D. C., Baek, S. W., Cho, D. Y., Choi, J. G., & Kang, J. (2018) · Cancer Management and Research · doi:10.2147/cmar.s174966 · Cited by 16
“Many other mTOR inhibitors are being developed for clinical and preclinical studies.(28) Recently, an Australian skin cancer trial showed that cutaneous SCC occurred at a significantly lower rate in the sirolimus group of transplant patients over a 2-year observation period.”
Background
mTOR-coordinated Post-Transcriptional Gene Regulations: from Fundamental to Pathogenic Insights
Yeh, H.-S., & Yong, J. (2020) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2020.9.1.8 · Cited by 15
Evaluation of Kaempferol as AKT Dependent mTOR Regulator via Targeting FKBP-12 in Hepatocellular Carcinoma: An In silico Approach
Siniprasad, P., Nair, B., Balasubramaniam, V., Sadanandan, P., Namboori, P. K., & Nath, L. R. (2020) · Letters in Drug Design & Discovery · doi:10.2174/1570180817999200623115703 · Cited by 15
Nanodelivery Systems Face Challenges and Limitations in Bone Diseases Management
Giordano, F., Lenna, S., Rampado, R., Brozovich, A., Hirase, T., Tognon, M. G., Martini, F., Agostini, M., Yustein, J. T., & Taraballi, F. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202100152 · Cited by 17
NMR in integrated biophysical drug discovery for RAS: past, present, and future
Marshall, C. B., KleinJan, F., Gebregiworgis, T., Lee, K., Fang, Z., Eves, B. J., Liu, N. F., Gasmi-Seabrook, G. M. C., Enomoto, M., & Ikura, M. (2020) · Journal of Biomolecular NMR · doi:10.1007/s10858-020-00338-6 · Cited by 15
“Structural similarity between PI3K and mTOR kinase domains facilitated the development of dual pan-PI3K/mTOR ATPcompetitive inhibitors such as dactolisib (Xie et al. 2016), which may help counteract the release of negative feedback loops involving both PI3K and mTOR.”
Background
MYC‐binding lncRNA EPIC1 promotes AKT‐mTORC1 signaling and rapamycin resistance in breast and ovarian cancer
Wang, Y., Zhang, M., Wang, Z., Guo, W., & Yang, D. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23248 · Cited by 14
“Previous studies also showed that drug resistance exists in patients who treated with rapamycin derivatives and other types of mTOR inhibitors.[41, 42] To overcome mTOR inhibitors’ drug”
Background
Molecular recognition of some novel mTOR kinase inhibitors to develop anticancer leads by drug-likeness, molecular docking and molecular dynamics based virtual screening strategy
Das, A., Matada, G. S. P., Dhiwar, P. S., Raghavendra, N. M., Abbas, N., Singh, E., Ghara, A., & Shenoy, G. P. (2022) · Computational Toxicology · doi:10.1016/j.comtox.2022.100257 · Cited by 13
The Role of Proteomics and Phosphoproteomics in the Discovery of Therapeutic Targets and Biomarkers in Acquired EGFR-TKI-Resistant Non-Small Cell Lung Cancer
Moonmuang, S., Tantraworasin, A., Orrapin, S., Udomruk, S., Chewaskulyong, B., Pruksakorn, D., & Chaiyawat, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054827 · Cited by 12
“The mTOR inhibitors, including everolimus, have been approved for cancer treatment including neuroendocrine tumors and, as a combination therapy, HER2-positive breast cancer, as well as certain tuberous sclerosis complex-related tumors [96].”
Background
The impact of exogenous CO releasing molecule CORM‑2 on inflammation and signaling of orthotopic lung cancer
Shao, L. W., Liu, C., Wang, S., Liu, J., Wang, L., Lv, L., & Zou, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.9022 · Cited by 12
“…mitigation of emboli formation, accompanied with extensive The AKT/mTOR signaling pathway is frequently aberrantly activated in human lung cancer (29), and transmits upstream proliferation signals via a phosphorylation cascade, eventually stimulating the transcription of effectors down-stream.”
GSK3β suppression inhibits MCL1 protein synthesis in human acute myeloid leukemia cells
Lee, Y., Shi, Y., Wang, L., Chiou, J., Huang, C., & Chang, L. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29884 · Cited by 12
“Although advances in genomics and molecular biology have improved the understanding of molecular pathogenesis of AML, standard therapy for AML exhibits limited progress (Watts & Nimer, 2018; X. Yang & Wang, 2018).”
Background
Therapeutic Approach of KRAS Mutant Tumours by the Combination of Pharmacologic Ascorbate and Chloroquine
Kapuy, O., Makk‐Merczel, K., & Szarka, A. (2021) · Biomolecules · doi:10.3390/biom11050652 · Cited by 13
“In addition, the mTOR pathway also enhances aerobic glycolysis by upregulating PKM2 via c-Myc induction [28], suggesting that inhibition of the mTOR pathway by pharmacological components (such as RapaLinks [29]) might have therapeutic importance in cancer treatment.”
Background
SMG1 , a nonsense‐mediated mRNA decay ( NMD ) regulator, as a candidate therapeutic target in multiple myeloma
Leeksma, A. C., Derks, I. A. M., Garrick, B., Jongejan, A., Colombo, M., Bloedjes, T. A., Trowe, T., Leisten, J. C., Howarth, M., Malek, M., et al. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13343 · Cited by 11
Exosomes derived from rapamycin‐treated 4T1 breast cancer cells induced polarization of macrophages to M1 phenotype
Ghalavand, M., Moradi‐Chaleshtori, M., Dorostkar, R., Mohammadi‐Yeganeh, S., & Hashemi, S. M. (2023) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.2473 · Cited by 11
Defective Protein Catabolism in Atherosclerotic Vascular Inflammation
Miyazaki, T., & Miyazaki, A. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00079 · Cited by 11
Tumor Microenvironment Modulates Immunological Outcomes of Myeloid Cells with mTORC1 Disruption
Ding, C., Sun, X., Wu, C., Hu, X., Zhang, H., & Yan, J. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801112 · Cited by 14
Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound
Nayeem, N., Sauma, S., Ahad, A., Rameau, R. D., Kebadze, S., Bazett, M., Park, B., Casaccia, P., Prabha, S., Hubbard, K., et al. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.4c00020 · Cited by 10
mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell Carcinoma
Lee, H. J., Shin, D., Song, J. S., Park, J. Y., Kim, S. Y., Hwang, C., Na, J., Lee, J. H., Kim, J. Y., Park, S. W., et al. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.07.007 · Cited by 10
Translational Regulation in Hepatocellular Carcinogenesis
Bračič, S., Schatz, C., & Haybaeck, J. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s255582 · Cited by 10
Cell-cell interactions that drive tumorigenesis in Drosophila
Enomoto, M., & Igaki, T. (2022) · Fly · doi:10.1080/19336934.2022.2148828 · Cited by 10
In vitro and computational studies showed that perezone inhibits PARP-1 and induces changes in the redox state of K562 cells
Rodríguez, M. H., Sánchez, P. I. M., Pérez, M. E. M., Cruz, E. R., Jiménez, E. M., Nicolás‐Vázquez, M. I., & Ruvalcaba, R. M. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.05.002 · Cited by 10
Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex
Lu, Y., Zhang, E. Y., Liu, J., & Yu, J. J. (2020) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-020-01490-w · Cited by 10
“Rapamycin (sirolimus) acts by forming complex with the intracellular binding protein FK506-binding protein (FKBP121), such complex in turn binds to the FKBP12rapamycin binding (FRB) domain of the mTORC1 molecule to inhibit mTORC1 activity [38, 39].”
Background
Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets
Yu, P.-C., Huang, C.-H., Kuo, C., Liang, P., Wang, L. H.-C., Pan, M. Y.-C., Chang, S., Chao, T., Ieong, S., Fang, J., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14010176 · Cited by 10
“In recent years, numerous studies revealed that sirolimus has therapeutic effects on many types of cancer [53].”
Background
IRF3 and IRF7 contribute to diesel exhaust particles‐induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice
Li, Y., Wang, C., Wu, X., Tian, H., Jiang, S., Xu, T., Liu, Z., Sun, J., & Qi, X. (2020) · European Journal of Immunology · doi:10.1002/eji.201948415 · Cited by 10
Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors
Pinto, D. O., DeMarino, C., Vo, T. T., Cowen, M., Kim, Y., Pleet, M. L., Barclay, R. A., Hooten, N. N., Evans, M. K., Heredia, A., et al. (2020) · Viruses · doi:10.3390/v12080885 · Cited by 10
“The mTOR complexes can be pharmacologically inhibited by mTORi to promote the autophagy pathway and have been approved for use in the treatment of cancer [79,85,86].”
Background
A ketogenic diet alters mTOR activity, systemic metabolism and potentially prevents collagen degradation associated with chronic alcohol consumption in mice
Willemse, L., Terburgh, K., & Louw, R. (2023) · Metabolomics · doi:10.1007/s11306-023-02006-w · Cited by 9
“Accordingly, administration of the potent mTOR inhibitor, rapamycin, has been reported to prevent epilepsy, disrupt tumour metabolism as well as impair mitochondrial disease progression in various animal models (Johnson et al., 2013; Xie et al., 2016; Zeng et al., 2008).”
Background
Novel BRET combination for detection of rapamycin-induced protein dimerization using luciferase from fungus Neonothopanus nambi
Mujawar, A., Dimri, S., Palkina, K. A., Markina, N. M., Sarkisyan, K. S., Balakireva, A. V., Yampolsky, I. V., & De, A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25553 · Cited by 9
“For further validation of the TFFH sensor specificity, we introduced two point mutations: A2034V and F2108L in the rapamycin-binding site of FRB domain using site-directed mutagenesis [24,25].”
Method
TSC-insensitive Rheb mutations induce oncogenic transformation through a combination of constitutively active mTORC1 signalling and proteome remodelling
Xie, J., Poi, S. P. D., Humphrey, S. J., Hein, L. K., Bruning, J. B., Pan, W., Selth, L. A., Sargeant, T. J., & Proud, C. G. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03825-7 · Cited by 9
“As hyperactive mTORC1 signalling occurs in multiple cancers [31], we hypothesised that Rheb mutants that drive hyperactive mTORC1 signalling may be oncogenic”
Background
Overview of Current and Future Adjuvant Therapy for High-Risk Localized Renal Cell Carcinoma
Nandagopal, L., Naik, G., & Sonpavde, G. (2018) · Current Treatment Options in Oncology · doi:10.1007/s11864-018-0522-4 · Cited by 9
Discovery and optimization of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives as mTORC1/mTORC2 dual inhibitors
Hu, S., Zhao, Z., & Yan, H. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103232 · Cited by 9
COX-2 Promotes Metastasis and Predicts Prognosis in Gastric Cancer via Regulating mTOR
Xiang, L., Wang, W., Zhou, Z., Lv, M., Li, T., Ni, T., Deng, J., Masatara, S., Liu, Y., & Zhou, Y. (2020) · Biomarkers in Medicine · doi:10.2217/bmm-2019-0357 · Cited by 9
RICTOR Amplification Promotes NSCLC Cell Proliferation through Formation and Activation of mTORC2 at the Expense of mTORC1
Kim, L. C., Rhee, C. H., & Chen, J. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-0262 · Cited by 9
“However, only mTORC1specific inhibitors (rapamycin analogues) or mTOR kinase inhibitors that block the activity of both complexes are available (33).”
Background
The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential
Baskarapantula, S. S., Kumar, V. S., Changdar, P., Chakraborty, D., Nayak, Y., Spada, A. R. L., Bennett, C. L., & Dastidar, S. G. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05553-6 · Cited by 8
“These inhibitors cannot completely inhibit mTORC1 and weakly inhibit the mTORC2 complex [238, 242, 244].”
Dual role of autophagy for advancements from conventional to new delivery systems in cancer
Mehta, P., & Shende, P. K. (2023) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2023.130430 · Cited by 8
Pharmacological effects of mTORC1/C2 inhibitor in a preclinical model of NASH progression
Arora, M., Pavlíková, Z., Kučera, T., Kozlík, P., Šopin, T., Vacı́k, T., Ľupták, M., Duda, M., Slanař, O., & Canová, N. K. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115447 · Cited by 9
Impact of Dysfunctional Protein Catabolism on Macrophage Cholesterol Handling
Miyazaki, T., & Miyazaki, A. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180326165234 · Cited by 8
Surendra Nath Sehgal: A pioneer in rapamycin discovery
Samanta, D. (2017) · Indian Journal of Cancer · doi:10.4103/ijc.ijc_84_18 · Cited by 8
Rapamycin Combi with TAE on the Growth, Metastasis, and Prognosis of Hepatocellular Carcinoma in Rat Models
Lei, H.-W., Cai, J., Li, C., Yang, F., Wan-qing, S., Wang, L., & Feng, Y.-Y. (2018) · Annals of Hepatology · doi:10.5604/01.3001.0012.0948 · Cited by 8
Directly imaging the localisation and photosensitization properties of the pan-mTOR inhibitor, AZD2014, in living cancer cells
Ahmed, A. R., Candeo, A., D’Abrantes, S., Needham, S. R., Yadav, R. B., Botchway, S. W., & Parker, A. W. (2020) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2020.112055 · Cited by 8
“It is reported that mTOR is hyperactivated in almost 70% of all human cancers [17].”
Background
Everolimus worsening chronic proteinuria in patient with diabetic nephropathy post liver transplantation
Hanna, R. M., Yanny, B., Arman, F., Barsoum, M., Mikhail, M., Baghdadi, M. A., Rastogi, A., Wallace, W. D., & Saab, S. (2019) · Saudi Journal of Kidney Diseases and Transplantation · doi:10.4103/1319-2442.265481 · Cited by 7
Targeting mTORC1 Activity to Improve Efficacy of Radioligand Therapy in Cancer
Grzmil, M., Wiesmann, F., Schibli, R., & Béhé, M. P. (2022) · Cancers · doi:10.3390/cancers15010017 · Cited by 9
“PTEN antagonizes PI3K activity via the regulation of a second messenger in the plasma membrane, which recruits phosphoinositide-dependent kinase 1 (PDK1) required for AKT activation [37].”
BackgroundInfluential
Modulator of the PI3K/Akt oncogenic pathway affects mTOR complex 2 in human adenocarcinoma cells
Curless, B. P., Uko, N. E., & Matesic, D. F. (2018) · Investigational New Drugs · doi:10.1007/s10637-018-0705-7 · Cited by 7
“[44] The results from these third-generation mTOR inhibitors remain to be elucidated.”
Background
Development of ErbB2-Targeting Liposomes for Enhancing Drug Delivery to ErbB2-Positive Breast Cancer
Ueno, S., Kim, M. W., Lee, G., Park, Y. I., Niidome, T., & Lee, A. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12060585 · Cited by 7
The 3.2Å resolution structure of human mTORC2Preprint
Scaiola, A., Mangia, F., Imseng, S., Boehringer, D., Berneiser, K., Shimobayashi, M., Stuttfeld, E., Hall, M. N., Ban, N., & Maier, T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.10.029835 · Cited by 8

Authors: Xie, J., Wang, X., & Proud, C. G.
Affiliations: South Australian Health and Medical Research Institute (AU)
Corresponding author: Proud, Christopher G.
ORCID: Xie, Jianling
Wang, Xuemin
Proud, Christopher G.
Venue: F1000Research
Publisher: F1000 Research Ltd
Published: 2016-08-25
Volume: 5
Pages: 2078
ISSN: 2046-1402 (ISSN-L)
DOI: 10.12688/f1000research.9207.1
PMC: PMC5007757
OpenAlex: W2517175971
Cited by: 266
References: 84
Citations by year: 2026: 8 · 2025: 14 · 2024: 9 · 2023: 21 · 2022: 31 · 2021: 36 · 2020: 49 · 2019: 32 · 2018: 37 · 2017: 28 · 2016: 1
FWCI: 2.96
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: F1000Research (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: mTOR inhibitors, mammalian target of rapamycin, mTORC1, mTORC2, rapamycin, cancer therapy, cell growth and proliferation, oncogenic signaling, feedback loops, drug resistance

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