The DOI matches its Crossref record; 228 of the 234 references it cites were found in a registry or an index.
mTOR: Role in cancer, metastasis and drug resistance
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that gets inputs from the amino acids, nutrients, growth factor, and environmental cues to regulate varieties of fundamental cellular processes which include protein synthesis, growth, metabolism, aging, regeneration, autophagy, etc. The mTOR is frequently deregulated in human cancer and activating somatic mutations of mTOR were recently identified in several types of human cancer and hence mTOR is therapeutically targeted. mTOR inhibitors were commonly used as immunosuppressors and currently, it is approved for the treatment of human malignancies. This review briefly focuses on the structure and biological functions of mTOR. It extensively discusses the genetic deregulation of mTOR including amplifications and somatic mutations, mTOR-mediated cell growth promoting signaling, therapeutic targeting of mTOR and the mechanisms of resistance, the role of mTOR in precision medicine and other recent advances in further understanding the role of mTOR in cancer.
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“RAD001 is currently used to treat several cancers (53), including renal cell carcinoma (RCC) (54)”
From The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells (2022) · cites this paper as [53]
Citations
Cites
1 retracted
Zhou, X.-M., Sun, R., Luo, D., Sun, J., Zhang, M.-Y., Wang, M.-H., Yang, Y., Wang, H., & Mai, S. (2016) · Oncotarget · doi:10.18632/oncotarget.7215 · Cited by 66
RetractedIntratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
Epithelial–mesenchymal transitions in tumour progression
Thiery, J. P. (2002) · Nature reviews. Cancer · doi:10.1038/nrc822 · Cited by 6,767
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
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6 of the 234 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Davies, 2005, Somatic mutations of the protein kinase gene family in human lung cancer, Cancer Res., 65, 7591, 10.1158/0008-5472.CAN-05-1855 · DOI
- Sato, 2010, Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer, Oncogene, 29, 2746, 10.1038/onc.2010.28 · DOI
Cited by
Sorted by citations
Targeting PI3K/Akt signal transduction for cancer therapy
He, Y., Sun, M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 2,045
Panwar, V., Singh, A., Bhatt, M., Tonk, R. K., Azizov, S., Raza, A. S., Sengupta, S., Kumar, D., & Garg, M. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01608-z · Cited by 967
PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?
Peng, Y., Wang, Y., Zhou, C., Mei, W., & Zeng, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.819128 · Cited by 810
Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer
Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 818
Xu, F., Na, L., Li, Y., & Chen, L. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00416-0 · Cited by 542
Retracted
Metadata
- Authors
- Murugan, A. K.
- Affiliations
- King Faisal Specialist Hospital & Research Centre (SA)
- Corresponding author
- Murugan, Avaniyapuram Kannan
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 59
- Pages
- 92-111
- ISSN
- 1044-579X (ISSN-L)
- OpenAlex
- W2969086321
- Cited by
- 483
- References
- 234
- Citations by year
- 2026: 25 · 2025: 57 · 2024: 84 · 2023: 84 · 2022: 120 · 2021: 74 · 2020: 31 · 2019: 7
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mTOR, cancer, metastasis, drug resistance, mTOR inhibitors, somatic mutations, gene amplification, cell growth signaling, autophagy, precision medicine, immunosuppressants
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Animals, Disease Susceptibility, Enzyme Activation, Humans, Mutation, Neoplasm Metastasis, Neoplasm Staging, Neoplasms, Biomarkers, Tumor, Signal Transduction, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases, Molecular Targeted Therapy, Mutation Rate
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