Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
February-2026 Volume 68 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2026 Volume 68 Issue 2

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review)

  • Authors:
    • Xiao Pang
    • Huai Liu
    • Ying Long
    • Hui Wang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Translational Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine/Hunan Cancer Hospital, Central South University, Changsha, Hunan 410013, P.R. China
    Copyright: © Pang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 21
    |
    Published online on: December 8, 2025
       https://doi.org/10.3892/ijo.2025.5834
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Radiotherapy is an important treatment for tumors; however, some patients exhibit poor sensitivity to radiation, leading to unsatisfactory outcomes. mTOR regulates critical processes such as cell proliferation, autophagy and DNA repair, serving a central role in tumor biology. Moreover, mTOR inhibitors have shown potential to enhance radiotherapy effectiveness and address radiation resistance. Although drug resistance and side effects limit their clinical use, combining therapies and optimizing treatment plans could improve results. The present review summarizes how mTOR signaling contributes to radiation resistance in lung cancer, as well as the underlying molecular mechanisms. Understanding these pathways may aid the development of new combination therapies to improve treatment options for patients with lung cancer.
View Figures

Figure 1

Structure and functional domains of
mTORCs. (A) Schematic diagram illustrating the subunit compositions
of mTORC1 and mTORC2, including their core components and distinct
regulatory subunits. mTORC1 comprises six core subunits: mTOR,
Raptor, mLST8, PRAS40, Deptor and the Tti1/Tel2 complex. This
complex regulates cell proliferation via downstream effectors
(4EBP1, S6K1). mTORC2 consists of seven components: mTOR, Rictor,
mSIN1, Protor1/2, Deptor, mLST8 and Tti1/Tel2, and modulates
cytoskeletal dynamics, cell survival and cell proliferation through
AKT, SGK1 and PKC. (B) Structural schematic diagrams highlighting
subunit arrangements. mTORC1 is depicted with Raptor, PRAS40, and
the FRB domain, while mTORC2 shows Rictor and mSIN1. Diagrams
illustrate distinct architectural features, including
Raptor-mediated substrate recruitment in mTORC1 and
Rictor-dependent membrane localization in mTORC2. Deptor, DEP
domain-containing mTOR-interacting protein; FAT, focal adhesion
targeting; FRB, FKBP12-rapamycin binding; mSIN1, mammalian
stress-activated protein kinase-interacting protein 1; mTORC, mTOR
complex; PRAS40, proline-rich AKT substrate of 40 kDa; Raptor,
regulatory-associated protein of mTOR; Rictor,
rapamycin-insensitive companion of mTOR; S6K1, S6 kinase 1.

Figure 2

PI3K/AKT/mTOR pathway-mediated
molecular mechanisms underlying lung cancer radioresistance.
Irradiated lung tumor cells activate the PI3K/AKT/mTOR pathway,
which inhibits autophagy, promotes metabolism and acts on DNA-PKcs
to influence DSB repair, mediating radioresistance in lung cancer
cells. DNA-PKcs, DNA-dependent protein kinase catalytic subunit;
DSB, double-strand break; mTORC, mTOR complex.

Figure 3

Mechanisms of mTOR in lung cancer
radioresistance and therapeutic targets. In lung cancer, mTOR acts
as a central hub driving radioresistance; it enhances DNA repair
via regulating DNA-PKcs, modulates autophagy to support cellular
survival, influences miRNA expression, mediates metabolic
resilience in small cell lung cancer through G6PD degradation, and
upregulates PD-L1 to facilitate immune evasion. Radioresistance
nodes, marked by red in the figure, refer to a key molecular
component or pathway where mTOR signaling promotes radioresistance,
such as DNA repair, autophagy and PD-L1-mediated immune evasion.
Therapeutic targets focus on disrupting these mTOR-driven pathways,
including direct inhibition of mTOR, targeting its upstream
PI3K/AKT axis, regulating autophagy, or combining mTOR inhibitors
with anti-PD-1/PD-L1. DNA-PKcs, DNA-dependent protein kinase
catalytic subunit; G6PD, glucose-6-phosphate dehydrogenase; miRNA,
microRNA; PDCD4, programmed cell death 4; PD-L1, programmed
death-ligand 1; ROS, reactive oxygen species; RTK, receptor
tyrosine kinase.
View References

1 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024.PubMed/NCBI

2 

Lehrer EJ, Singh R, Wang M, Chinchilli VM, Trifiletti DM, Ost P, Siva S, Meng MB, Tchelebi L and Zaorsky NG: Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: A systematic review and meta-analysis. JAMA Oncol. 7:92–106. 2021. View Article : Google Scholar

3 

Gonsalves D, Ocanto A, Martín M and Couñago F: Radiotherapy in early stages of lung cancer. Revisiones en Cancer. 37:133–147. 2023.

4 

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD and Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Bache M, Kadler F, Struck O, Medenwald D, Ostheimer C, Güttler A, Keßler J, Kappler M, Riemann A, Thews O, et al: Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy response and survival of non-small-cell lung cancer patients. Int J Mol Sci. 24:128352023. View Article : Google Scholar : PubMed/NCBI

6 

Laplante M and Sabatini DM: mTOR signaling in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Panwar V, Singh A, Bhatt M, Tonk RK, Azizov S, Raza AS, Sengupta S, Kumar D and Garg M: Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct Target Ther. 8:3752023. View Article : Google Scholar : PubMed/NCBI

8 

Wei F, Liu Y, Guo Y, Xiang A, Wang G, Xue X and Lu Z: MiR-99b-targeted mTOR induction contributes to irradiation resistance in pancreatic cancer. Mol Cancer. 12:812013. View Article : Google Scholar : PubMed/NCBI

9 

Woo Y, Lee HJ, Jung YM and Jung YJ: MTOR-mediated antioxidant activation in solid tumor radioresistance. J Oncol. 2019:59568672019. View Article : Google Scholar

10 

Yu CC, Hung SK, Lin HY, Chiou WY, Lee MS, Liao HF, Huang HB, Ho HC and Su YC: Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo. Oncotarget. 8:68641–68653. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Wanigasooriya K, Tyler R, Barros-Silva JD, Sinha Y, Ismail T and Beggs AD: Radiosensitising cancer using phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT) or mammalian target of rapamycin (mTOR) inhibitors. Cancers (Basel). 12:12782020. View Article : Google Scholar : PubMed/NCBI

12 

Mardanshahi A, Gharibkandi NA, Vaseghi S, Abedi SM and Molavipordanjani S: The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines. Mol Biol Rep. 48:1–14. 2021. View Article : Google Scholar : PubMed/NCBI

13 

Feng YQ, Gu SX, Chen YS, Gao XD, Ren YX, Chen JC, Lu YY, Zhang H and Cao S: Virtual screening and optimization of novel mTOR inhibitors for radiosensitization of hepatocellular carcinoma. Drug Des Devel Ther. 14:1779–1798. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Ihlamur M, Akgül B, Zengin Y, Korkut ŞV, Kelleci K and Abamor EŞ: The mTOR signaling pathway and mTOR inhibitors in cancer: Next-generation inhibitors and approaches. Curr Mol Med. 24:478–494. 2024. View Article : Google Scholar

15 

Vézina C, Kudelski A and Sehgal SN: Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo). 28:721–726. 1975. View Article : Google Scholar : PubMed/NCBI

16 

Pignataro G, Capone D, Polichetti G, Vinciguerra A, Gentile A, Di Renzo G and Annunziato L: Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: Current and emerging therapeutic options. Curr Opin Pharmacol. 11:378–394. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Drenan RM, Liu X, Bertram PG and Zheng XF: FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi apparatus. J Biol Chem. 279:772–778. 2004. View Article : Google Scholar

18 

Helfenberger KE, Argentino GF, Benzo Y, Herrera LM, Finocchietto P and Poderoso C: Angiotensin II regulates mitochondrial mTOR pathway activity dependent on Acyl-CoA synthetase 4 in adrenocortical cells. Endocrinology. 163:bqac1702022. View Article : Google Scholar : PubMed/NCBI

19 

Chen Y and Zhou X: Research progress of mTOR inhibitors. Eur J Med Chem. 208:1128202020. View Article : Google Scholar : PubMed/NCBI

20 

Ali M, Bukhari SA, Ali M and Lee HW: Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D). BMB Rep. 50:601–609. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Wang G, Chen L, Qin S, Zhang T, Yao J, Yi Y and Deng L: Mechanistic target of rapamycin complex 1: From a nutrient sensor to a key regulator of metabolism and health. Adv Nutr. 13:1882–1900. 2022. View Article : Google Scholar : PubMed/NCBI

22 

Workman JJ, Chen H and Laribee RN: Environmental signaling through the mechanistic target of rapamycin complex 1: mTORC1 goes nuclear. Cell Cycle. 13:714–725. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Yoon MS: The role of mammalian target of rapamycin (mTOR) in insulin signaling. Nutrients. 9:11762017. View Article : Google Scholar : PubMed/NCBI

24 

Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, et al: Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 335:1638–1643. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL and Sabatini DM: Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell. 22:159–168. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Wang W, Tan J, Liu X, Guo W, Li M, Liu X, Liu Y, Dai W, Hu L, Wang Y, et al: Cytoplasmic endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress. Nat Commun. 14:62012023. View Article : Google Scholar : PubMed/NCBI

27 

Peng H, Kasada A, Ueno M, Hoshii T, Tadokoro Y, Nomura N, Ito C, Takase Y, Vu HT, Kobayashi M, et al: Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells. Biochem Biophys Res Commun. 495:1129–1135. 2018. View Article : Google Scholar

28 

Miricescu D, Totan A, Stanescu-Spinu II, Badoiu SC, Stefani C and Greabu M: PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects. Int J Mol Sci. 22:1732020. View Article : Google Scholar : PubMed/NCBI

29 

Inoki K, Kim J and Guan KL: AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol. 52:381–400. 2012. View Article : Google Scholar

30 

Chun Y and Kim J: AMPK-mTOR signaling and cellular adaptations in hypoxia. Int J Mol Sci. 22:97652021. View Article : Google Scholar : PubMed/NCBI

31 

Lama-Sherpa TD, Jeong MH and Jewell JL: Regulation of mTORC1 by the Rag GTPases. Biochem Soc Trans. 51:655–664. 2023. View Article : Google Scholar : PubMed/NCBI

32 

Kim SJ, DeStefano MA, Oh WJ, Wu CC, Vega-Cotto NM, Finlan M, Liu D, Su B and Jacinto E: mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the ubiquitin ligase subunit Fbw8. Mol Cell. 48:875–887. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Sural-Fehr T, Singh H, Cantuti-Catelvetri L, Zhu H, Marshall MS, Rebiai R, Jastrzebski MJ, Givogri MI, Rasenick MM and Bongarzone ER: Inhibition of the IGF-1-PI3K-Akt-mTORC2 pathway in lipid rafts increases neuronal vulnerability in a genetic lysosomal glycosphingolipidosis. Dis Model Mech. 12:dmm0365902019. View Article : Google Scholar : PubMed/NCBI

34 

Lazorchak AS and Su B: Perspectives on the role of mTORC2 in B lymphocyte development, immunity and tumorigenesis. Protein Cell. 2:523–530. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Li X and Gao T: mTORC2 phosphorylates protein kinase Cζ to regulate its stability and activity. EMBO Rep. 15:191–198. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Baffi TR, Lordén G, Wozniak JM, Feichtner A, Yeung W, Kornev AP, King CC, Del Rio JC, Limaye AJ, Bogomolovas J, et al: mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif. Sci Signal. 14:eabe45092021. View Article : Google Scholar : PubMed/NCBI

37 

Carter CC, Mast FD, Olivier JP, Bourgeois NM, Kaushansky A and Aitchison JD: Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication. Front Cell Infect Microbiol. 12:9799962022. View Article : Google Scholar : PubMed/NCBI

38 

Katholnig K, Schütz B, Fritsch SD, Schörghofer D, Linke M, Sukhbaatar N, Matschinger JM, Unterleuthner D, Hirtl M, Lang M, et al: Inactivation of mTORC2 in macrophages is a signature of colorectal cancer that promotes tumorigenesis. JCI Insight. 4:e1241642019. View Article : Google Scholar : PubMed/NCBI

39 

Mehta D, Rajput K, Jain D, Bajaj A and Dasgupta U: Unveiling the role of mechanistic target of rapamycin kinase (MTOR) signaling in cancer progression and the emergence of MTOR inhibitors as therapeutic strategies. ACS Pharmacol Transl Sci. 7:3758–3779. 2024. View Article : Google Scholar : PubMed/NCBI

40 

Qiu W, Ren M, Wang C, Fu Y and Liu Y: The clinicopathological and prognostic significance of mTOR and p-mTOR expression in patients with non-small cell lung cancer: A meta-analysis. Medicine (Baltimore). 101:e323402022. View Article : Google Scholar

41 

Zeng AQ, Chen X, Dai Y and Zhao JN: Betulinic acid inhibits non-small cell lung cancer by repolarizing tumor-associated macrophages via mTOR signaling pathway. Zhongguo Zhong Yao Za Zhi. 49:2376–2384. 2024.In Chinese. PubMed/NCBI

42 

Granville CA, Warfel N, Tsurutani J, Hollander MC, Robertson M, Fox SD, Veenstra TD, Issaq HJ, Linnoila RI and Dennis PA: Identification of a highly effective rapamycin schedule that markedly reduces the size, multiplicity, and phenotypic progression of tobacco carcinogen-induced murine lung tumors. Clin Cancer Res. 13:2281–2289. 2007. View Article : Google Scholar : PubMed/NCBI

43 

Raskova Kafkova L, Mierzwicka JM, Chakraborty P, Jakubec P, Fischer O, Skarda J, Maly P and Raska M: NSCLC: From tumorigenesis, immune checkpoint misuse to current and future targeted therapy. Front Immunol. 15:13420862024. View Article : Google Scholar : PubMed/NCBI

44 

Bang J, Jun M, Lee S, Moon H and Ro SW: Targeting EGFR/PI3K/AKT/mTOR signaling in hepatocellular carcinoma. Pharmaceutics. 15:21302023. View Article : Google Scholar : PubMed/NCBI

45 

Wu YY, Wu HC, Wu JE, Huang KY, Yang SC, Chen SX, Tsao CJ, Hsu KF, Chen YL and Hong TM: The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status, as a potent accompanist in combined therapeutic regimens. J Exp Clin Cancer Res. 38:2822019. View Article : Google Scholar : PubMed/NCBI

46 

Xu L, Ding R, Song S, Liu J, Li J, Ju X and Ju B: Single-cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation. J Gene Med. 26:e36582024. View Article : Google Scholar : PubMed/NCBI

47 

Ducray SP, Natarajan K, Garland GD, Turner SD and Egger G: The transcriptional roles of ALK fusion proteins in tumorigenesis. Cancers (Basel). 11:10742019. View Article : Google Scholar : PubMed/NCBI

48 

Zhao T, Fan J, Abu-Zaid A, Burley SK and Zheng XFS: Nuclear mTOR signaling orchestrates transcriptional programs underlying cellular growth and metabolism. Cells. 13:7812024. View Article : Google Scholar : PubMed/NCBI

49 

Zhang Q, Zhang Y, Chen Y, Qian J, Zhang X and Yu K: A Novel mTORC1/2 Inhibitor (MTI-31) inhibits tumor growth, epithelial-mesenchymal transition, metastases, and improves antitumor immunity in preclinical models of lung cancer. Clin Cancer Res. 25:3630–3642. 2019. View Article : Google Scholar : PubMed/NCBI

50 

Marinov M, Ziogas A, Pardo OE, Tan LT, Dhillon T, Mauri FA, Lane HA, Lemoine NR, Zangemeister-Wittke U, Seckl MJ and Arcaro A: AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001. Clin Cancer Res. 15:1277–1287. 2009. View Article : Google Scholar : PubMed/NCBI

51 

Li X, Li C, Guo C, Zhao Q, Cao J, Huang HY, Yue M, Xue Y, Jin Y, Hu L and Ji H: PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer. J Genet Genomics. 48:640–651. 2021. View Article : Google Scholar : PubMed/NCBI

52 

He C: Activating invasion and metastasis in small cell lung cancer: Role of the tumour immune microenvironment and mechanisms of vasculogenesis, epithelial-mesenchymal transition, cell migration, and organ tropism. Cancer Rep (Hoboken). 7:e700182024.

53 

Fiorentino FP, Tokgün E, Solé-Sánchez S, Giampaolo S, Tokgün O, Jauset T, Kohno T, Perucho M, Soucek L and Yokota J: Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation. Oncotarget. 7:31014–31028. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Matsumoto M, Seike M, Noro R, Soeno C, Sugano T, Takeuchi S, Miyanaga A, Kitamura K, Kubota K and Gemma A: Control of the MYC-eIF4E axis plus mTOR inhibitor treatment in small cell lung cancer. BMC Cancer. 15:2412015. View Article : Google Scholar : PubMed/NCBI

55 

Chang L, Graham PH, Ni J, Hao J, Bucci J, Cozzi PJ and Li Y: Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol. 96:507–517. 2015. View Article : Google Scholar : PubMed/NCBI

56 

Liu N and Wang P: Development of PI3K/AKT/mTOR signaling pathway and hypofractionated radiotherapy in non-small cell lung cancer. Chin J Clin Oncol. 40:1196–1198. 2013.In Chinese.

57 

Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, Eng H, Nair MG, Makvandi P, Geoerger B, et al: PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 22:1382023. View Article : Google Scholar : PubMed/NCBI

58 

Sarbassov DD, Guertin DA, Ali SM and Sabatini DM: Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 307:1098–1101. 2005. View Article : Google Scholar : PubMed/NCBI

59 

Huang J, Chen L, Wu J, Ai D, Zhang JQ, Chen TG and Wang L: Targeting the PI3K/AKT/mTOR signaling pathway in the treatment of human diseases: Current status, trends, and solutions. J Med Chem. 65:16033–16061. 2022. View Article : Google Scholar : PubMed/NCBI

60 

Schuurbiers OC, Kaanders JH, van der Heijden HF, Dekhuijzen RP, Oyen WJ and Bussink J: The PI3-K/AKT-pathway and radiation resistance mechanisms in non-small cell lung cancer. J Thorac Oncol. 4:761–767. 2009. View Article : Google Scholar : PubMed/NCBI

61 

Toulany M, Iida M, Keinath S, Iyi FF, Mueck K, Fehrenbacher B, Mansour WY, Schaller M, Wheeler DL and Rodemann HP: Dual targeting of PI3K and MEK enhances the radiation response of K-RAS mutated non-small cell lung cancer. Oncotarget. 7:43746–43761. 2016. View Article : Google Scholar : PubMed/NCBI

62 

Zhang T, Cui GB, Zhang J, Zhang F, Zhou YA, Jiang T and Li XF: Inhibition of PI3 kinases enhances the sensitivity of non-small cell lung cancer cells to ionizing radiation. Oncol Rep. 24:1683–1689. 2010.PubMed/NCBI

63 

Chen K, Shang Z, Dai AL and Dai PL: Novel PI3K/Akt/mTOR pathway inhibitors plus radiotherapy: Strategy for non-small cell lung cancer with mutant RAS gene. Life Sci. 255:1178162020. View Article : Google Scholar : PubMed/NCBI

64 

Kim SY, Jeong EH, Lee TG, Kim HR and Kim CH: The combination of trametinib, a MEK inhibitor, and temsirolimus, an mTOR Inhibitor, radiosensitizes lung cancer cells. Anticancer Res. 41:2885–2894. 2021. View Article : Google Scholar : PubMed/NCBI

65 

He GH, Xing DJ, Jin D, Lu Y, Guo L, Li YL and Li D: Scutellarin improves the radiosensitivity of non-small cell lung cancer cells to iodine-125 seeds via downregulating the AKT/mTOR pathway. Thorac Cancer. 12:2352–2359. 2021. View Article : Google Scholar : PubMed/NCBI

66 

Sebastian NT, Webb A, Shilo K, Robb R, Xu-Welliver M, Haglund K, Brownstein J, DeNicola GM, Shen C and Williams TM: A PI3K gene expression signature predicts for recurrence in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy. Cancer. 129:3971–3977. 2023. View Article : Google Scholar : PubMed/NCBI

67 

Choi EJ, Ryu YK, Kim SY, Wu HG, Kim JS, Kim IH and Kim IA: Targeting epidermal growth factor receptor-associated signaling pathways in non-small cell lung cancer cells: Implication in radiation response. Mol Cancer Res. 8:1027–1036. 2010. View Article : Google Scholar : PubMed/NCBI

68 

Holler M, Grottke A, Mueck K, Manes J, Jücker M, Rodemann HP and Toulany M: Dual Targeting of Akt and mTORC1 impairs repair of DNA double-strand breaks and increases radiation sensitivity of human tumor cells. PLoS One. 11:e01547452016. View Article : Google Scholar : PubMed/NCBI

69 

Zhang P, He D, Song E, Jiang M and Song Y: Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression. PLoS One. 14:e02237602019. View Article : Google Scholar : PubMed/NCBI

70 

Xiong L, Tan B, Lei X, Zhang B, Li W, Liu D and Xia T: SIRT6 through PI3K/Akt/mTOR signaling pathway to enhance radiosensitivity of non-Small cell lung cancer and inhibit tumor progression. IUBMB Life. 73:1092–1102. 2021. View Article : Google Scholar : PubMed/NCBI

71 

Hamid MB, Serafin AM and Akudugu JM: Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells. Eur J Pharmacol. 912:1746122021. View Article : Google Scholar : PubMed/NCBI

72 

Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI

73 

Biswas U, Roy R, Ghosh S and Chakrabarti G: The interplay between autophagy and apoptosis: Its implication in lung cancer and therapeutics. Cancer Lett. 585:2166622024. View Article : Google Scholar : PubMed/NCBI

74 

Gargalionis AN, Papavassiliou KA and Papavassiliou AG: Implication of mTOR Signaling in NSCLC: Mechanisms and therapeutic perspectives. Cells. 12:20142023. View Article : Google Scholar : PubMed/NCBI

75 

Loizzo D, Pandolfo SD, Rogers D, Cerrato C, di Meo NA, Autorino R, Mirone V, Ferro M, Porta C, Stella A, et al: Novel insights into autophagy and prostate cancer: A comprehensive review. Int J Mol Sci. 23:38262022. View Article : Google Scholar : PubMed/NCBI

76 

Wang J, Gong M, Fan X, Huang D, Zhang J and Huang C: Autophagy-related signaling pathways in non-small cell lung cancer. Mol Cell Biochem. 477:385–393. 2022. View Article : Google Scholar

77 

Kim KW, Hwang M, Moretti L, Jaboin JJ, Cha YI and Lu B: Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer. Autophagy. 4:659–668. 2008. View Article : Google Scholar : PubMed/NCBI

78 

Fei HR, Tian H, Zhou XL, Yang MF, Sun BL, Yang XY, Jiao P and Wang FZ: Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells. Int J Biochem Cell Biol. 78:52–62. 2016. View Article : Google Scholar : PubMed/NCBI

79 

Yan J, Xie Y, Wang F, Chen Y, Zhang J, Dou Z, Gan L, Li H, Si J, Sun C, et al: Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction. Life Sci. 263:1185862020. View Article : Google Scholar : PubMed/NCBI

80 

Kim KW, Moretti L, Mitchell LR, Jung DK and Lu B: Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res. 15:6096–6105. 2009. View Article : Google Scholar : PubMed/NCBI

81 

Kim EJ, Jeong JH, Bae S, Kang S, Kim CH and Lim YB: mTOR inhibitors radiosensitize PTEN-deficient non-small-cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy. J Cell Biochem. 114:1248–1256. 2013. View Article : Google Scholar : PubMed/NCBI

82 

Kim KW, Myers CJ, Jung DK and Lu B: NVP-BEZ-235 enhances radiosensitization via blockade of the PI3K/mTOR pathway in cisplatin-resistant non-small cell lung carcinoma. Genes Cancer. 5:293–302. 2014. View Article : Google Scholar : PubMed/NCBI

83 

Liang N, Zhong R, Hou X, Zhao G, Ma S, Cheng G and Liu X: Ataxia-telangiectasia mutated (ATM) participates in the regulation of ionizing radiation-induced cell death via MAPK14 in lung cancer H1299 cells. Cell Prolif. 48:561–572. 2015. View Article : Google Scholar : PubMed/NCBI

84 

Zhang X, Ji J, Yang Y, Zhang J and Shen L: Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells. Onco Targets Ther. 9:2565–2574. 2016.PubMed/NCBI

85 

Lai C, Zhang J, Tan Z, Shen LF, Zhou RR and Zhang YY: Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. Aging (Albany NY). 13:7300–7313. 2021. View Article : Google Scholar : PubMed/NCBI

86 

He B, Zhao Z, Cai Q, Zhang Y, Zhang P, Shi S, Xie H, Peng X, Yin W, Tao Y and Wang X: Mirna-based biomarkers, therapies, and resistance in cancer. Int J Biol Sci. 6:2628–2647. 2020. View Article : Google Scholar

87 

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI

88 

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI

89 

Avvari S, Prasad DKV and Khan IA: Role of MicroRNAs in cell growth proliferation and tumorigenesis. Role of MicroRNAs in Cancers. Prasad D and Santosh Sushma P: Springer; Singapore: pp. 37–51. 2022, View Article : Google Scholar

90 

Chen Y, Li WW, Peng P, Zhao WH, Tian YJ, Huang Y, Xia S and Chen Y: mTORC1 inhibitor RAD001 (everolimus) enhances non-small cell lung cancer cell radiosensitivity in vitro via suppressing epithelial-mesenchymal transition. Acta Pharmacol Sin. 40:1085–1094. 2019. View Article : Google Scholar : PubMed/NCBI

91 

Yuan Y, Liao H, Pu Q, Ke X, Hu X, Ma Y, Luo X, Jiang Q, Gong Y, Wu M, et al: miR-410 induces both epithelial-mesenchymal transition and radioresistance through activation of the PI3K/mTOR pathway in non-small cell lung cancer. Signal Transduct Target Ther. 5:852020. View Article : Google Scholar : PubMed/NCBI

92 

Li T, Wei L, Zhang X, Fu B, Zhou Y, Yang M, Cao M, Chen Y, Tan Y, Shi Y, et al: Serotonin Receptor HTR2B facilitates colorectal cancer metastasis via CREB1-ZEB1 axis-mediated epithelial-mesenchymal transition. Mol Cancer Res. 22:538–554. 2024. View Article : Google Scholar : PubMed/NCBI

93 

Chen Y, Liao W, Yuan A, Xu H, Yuan R and Cao J: MiR-181a reduces radiosensitivity of non-small-cell lung cancer via inhibiting PTEN. Panminerva Med. 64:374–383. 2022. View Article : Google Scholar

94 

Jiang LP, He CY and Zhu ZT: Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by targeting PDCD4 gene. Oncotarget. 8:23675–23689. 2017. View Article : Google Scholar : PubMed/NCBI

95 

Huang M, Li T, Wang Q, Li C, Zhou H, Deng S, Lv Z, He Y, Hou B and Zhu G: Silencing circPVT1 enhances radiosensitivity in non-small cell lung cancer by sponging microRNA-1208. Cancer Biomark. 31:263–279. 2021. View Article : Google Scholar : PubMed/NCBI

96 

Yin H, Ma J, Chen L, Piao S, Zhang Y, Zhang S, Ma H, Li Y, Qu Y, Wang X and Xu Q: MiR-99a enhances the radiation sensitivity of non-small cell lung cancer by targeting mTOR. Cell Physiol Biochem. 46:471–481. 2018. View Article : Google Scholar : PubMed/NCBI

97 

Meng X, Sun Y, Liu S and Mu Y: miR-101-3p sensitizes lung adenocarcinoma cells to irradiation via targeting BIRC5. Oncol Lett. 21:2822021. View Article : Google Scholar : PubMed/NCBI

98 

Li Z, Qu Z, Wang Y, Qin M and Zhang H: miR-101-3p sensitizes non-small cell lung cancer cells to irradiation. Open Med (Wars). 15:413–423. 2020. View Article : Google Scholar : PubMed/NCBI

99 

Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, Chen G, Zhou Q, Wang W, Zhou X, et al: Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res. 35:72016. View Article : Google Scholar : PubMed/NCBI

100 

Deng H, Chen Y, Li P, Hang Q, Zhang P, Jin Y and Chen M: PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism: Potential targets to overcome radioresistance in small cell lung cancer. Cancer Pathog Ther. 1:56–66. 2023. View Article : Google Scholar

101 

Liu B, Huang ZB, Chen X, See YX, Chen ZK and Yao HK: Mammalian target of rapamycin 2 (MTOR2) and C-MYC modulate glucosamine-6-phosphate synthesis in glioblastoma (GBM) cells through glutamine: fructose-6-phosphate aminotransferase 1 (GFAT1). Cell Mol Neurobiol. 39:415–434. 2019. View Article : Google Scholar : PubMed/NCBI

102 

Deng H, Chen Y, Wang L, Zhang Y, Hang Q, Li P, Zhang P, Ji J, Song H, Chen M and Jin Y: PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer. Cell Death Dis. 14:6522023. View Article : Google Scholar : PubMed/NCBI

103 

Cardnell RJ, Feng Y, Mukherjee S, Diao L, Tong P, Stewart CA, Masrorpour F, Fan Y, Nilsson M, Shen Y, et al: Activation of the PI3K/mTOR pathway following PARP Inhibition in small cell lung cancer. PLoS One. 11:e01525842016. View Article : Google Scholar : PubMed/NCBI

104 

Knelson EH, Patel SA and Sands JM: PARP inhibitors in small-cell lung cancer: Rational combinations to improve responses. Cancers (Basel). 13:7272021. View Article : Google Scholar : PubMed/NCBI

105 

Kim WY, Oh SH, Woo JK, Hong WK and Lee HY: Targeting heat shock protein 90 overrides the resistance of lung cancer cells by blocking radiation-induced stabilization of hypoxia-inducible factor-1alpha. Cancer Res. 69:1624–1632. 2009. View Article : Google Scholar : PubMed/NCBI

106 

Subtil FS, Wilhelm J, Bill V, Westholt N, Rudolph S, Fischer J, Scheel S, Seay U, Fournier C, Taucher-Scholz G, et al: Carbon ion radiotherapy of human lung cancer attenuates HIF-1 signaling and acts with considerably enhanced therapeutic efficiency. FASEB J. 28:1412–1421. 2014. View Article : Google Scholar

107 

Jung MJ, Rho JK, Kim YM, Jung JE, Jin YB, Ko YG, Lee JS, Lee SJ, Lee JC and Park MJ: Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells. Oncogene. 32:209–221. 2013. View Article : Google Scholar

108 

Dodson M, Dai W, Anandhan A, Schmidlin CJ, Liu P, Wilson NC, Wei Y, Kitamura N, Galligan JJ, Ooi A, et al: CHML is an NRF2 target gene that regulates mTOR function. Mol Oncol. 16:1714–1727. 2022. View Article : Google Scholar : PubMed/NCBI

109 

Zheng H, Wang M, Wu J, Wang ZM, Nan HJ and Sun H: Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation. Biochem Cell Biol. 94:213–220. 2016. View Article : Google Scholar : PubMed/NCBI

110 

Lastwika KJ, Wilson W III, Li QK, Norris J, Xu H, Ghazarian SR, Kitagawa H, Kawabata S, Taube JM, Yao S, et al: Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer. Cancer Res. 76:227–238. 2016. View Article : Google Scholar

111 

Xiao P, Sun LL, Wang J, Han RL, Ma Q and Zhong DS: LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro. Acta Pharmacol Sin. 36:1107–1112. 2015. View Article : Google Scholar : PubMed/NCBI

112 

Li H, Li X, Liu S, Guo L, Zhang B, Zhang J and Ye Q: Programmed cell death-1 (PD-1) checkpoint blockade in combination with a mammalian target of rapamycin inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1. Hepatology. 66:1920–1933. 2017. View Article : Google Scholar : PubMed/NCBI

113 

Dong L, Lv H, Li W, Song Z, Li L, Zhou S, Qiu L, Qian Z, Liu X, Feng L, et al: Co-expression of PD-L1 and p-AKT is associated with poor prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular AKT/mTOR pathway in tumor cells. Oncotarget. 7:33350–33362. 2016. View Article : Google Scholar : PubMed/NCBI

114 

Chiarini F, Evangelisti C, McCubrey JA and Martelli AM: Current treatment strategies for inhibiting mTOR in cancer. Trends Pharmacol Sci. 36:124–135. 2015. View Article : Google Scholar

115 

Mohindra NA and Platanias LC: Catalytic mammalian target of rapamycin inhibitors as antineoplastic agents. Leuk Lymphoma. 56:2518–2523. 2015. View Article : Google Scholar : PubMed/NCBI

116 

Ushijima H, Suzuki Y, Oike T, Komachi M, Yoshimoto Y, Ando K, Okonogi N, Sato H, Noda SE, Saito J and Nakano T: Radio-sensitization effect of an mTOR inhibitor, temsirolimus, on lung adenocarcinoma A549 cells under normoxic and hypoxic conditions. J Radiat Res. 56:663–668. 2015. View Article : Google Scholar : PubMed/NCBI

117 

Chen H, Ma Z, Vanderwaal RP, Feng Z, Gonzalez-Suarez I, Wang S and Zhang J, Roti Roti JL, Gonzalo S and Zhang J: The mTOR inhibitor rapamycin suppresses DNA double-strand break repair. Radiat Res. 175:214–224. 2011. View Article : Google Scholar : PubMed/NCBI

118 

Waqar SN, Robinson C, Bradley J, Goodgame B, Rooney M, Williams K, Gao F and Govindan R: A phase I study of temsirolimus and thoracic radiation in non-small-cell lung cancer. Clin Lung Cancer. 15:119–123. 2014. View Article : Google Scholar : PubMed/NCBI

119 

Waldner M, Fantus D, Solari M and Thomson AW: New perspectives on mTOR inhibitors (rapamycin, rapalogs and TORKinibs) in transplantation. Br J Clin Pharmacol. 82:1158–1170. 2016. View Article : Google Scholar : PubMed/NCBI

120 

Dancey J: MTOR signaling and drug development in cancer. Nat Rev Clin Oncol. 7:209–219. 2010. View Article : Google Scholar : PubMed/NCBI

121 

Occhiuzzi MA, Lico G, Ioele G, De Luca M, Garofalo A and Grande F: Recent advances in PI3K/PKB/mTOR inhibitors as new anticancer agents. Eur J Med Chem. 246:1149712023. View Article : Google Scholar

122 

Waqar SN, Gopalan PK, Williams K, Devarakonda S and Govindan R: A phase I trial of sunitinib and rapamycin in patients with advanced non-small cell lung cancer. Chemotherapy. 59:8–13. 2013. View Article : Google Scholar : PubMed/NCBI

123 

Waqar SN, Baggstrom MQ, Morgensztern D, Williams K, Rigden C and Govindan R: A Phase I Trial of temsirolimus and pemetrexed in patients with advanced non-small cell lung cancer. Chemotherapy. 61:144–147. 2016. View Article : Google Scholar : PubMed/NCBI

124 

Riely GJ, Brahmer J, Planchard D, Crinò L, Doebele RC, Lopez LAM, Gettinger SN, Schumann C, Li X, Atkins BM, et al: A randomized discontinuation phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations. J Clin Oncol. 30(Suppl 15): 75322011.

125 

National Library of Medicine: Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors. Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL-19). ClinicalTrials.gov ID NCT05840510. https://clinicaltrials.gov/study/NCT05840510.

126 

Owonikoko TK, Ramalingam SS, Miller DL, Force SD, Sica GL, Mendel J, Chen Z, Rogatko A, Tighiouart M, Harvey RD, et al: A translational, pharmacodynamic, and pharmacokinetic phase IB clinical study of everolimus in resectable non-small cell lung cancer. Clin Cancer Res. 21:1859–1868. 2015. View Article : Google Scholar : PubMed/NCBI

127 

Bendell JC, Kelley RK, Shih KC, Grabowsky JA, Bergsland E, Jones S, Martin T, Infante JR, Mischel PS, Matsutani T, et al: A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma. Cancer. 121:3481–3490. 2015. View Article : Google Scholar : PubMed/NCBI

128 

Basu B, Dean E, Puglisi M, Greystoke A, Ong M, Burke W, Cavallin M, Bigley G, Womack C, Harrington EA, et al: First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor AZD2014. Clin Cancer Res. 21:3412–3419. 2015. View Article : Google Scholar : PubMed/NCBI

129 

Heist RS, Infante JR, Campana F, Egile C, Jego V, Damstrup L, Mita M, Grande E and Rizv N: 443O-Pimasertib (Pim) and Sar245409 (Sar)-a Mek and Pi3K/Mtor inhibitor combination: A Phase Ib trial with expansions in selected genotype-defined solid tumors. Ann Oncol. 25(Suppl 4): iv1462014. View Article : Google Scholar

130 

National Library of Medicine: Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung Pancreatic, Head & Neck Other Solid Tumors. ClinicalTrials.gov ID NCT03065062. https://clinicaltrials.gov/study/NCT03065062.

131 

McCay J and Gribben JG: PI3 kinase, AKT, and mTOR inhibitors. Precision Cancer Therapies. O'Connor OA, Ansell SM and Seymour JF: 1. John Wiley & Sons, Inc.; pp. 113–129. 2023

132 

Saran U, Foti M and Dufour JF: Cellular and molecular effects of the mTOR inhibitor everolimus. Clin Sci (Lond). 129:895–914. 2015. View Article : Google Scholar : PubMed/NCBI

133 

Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E, et al: Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 534:272–276. 2016. View Article : Google Scholar : PubMed/NCBI

134 

Porcelli L, Quatrale AE, Mantuano P, Silvestris N, Rolland JF, Biancolillo L, Paradiso A and Azzariti A: Synergistic antiproliferative and antiangiogenic effects of EGFR and mTOR inhibitors. Curr Pharm Des. 19:918–926. 2013. View Article : Google Scholar

135 

Weigelt B, Warne PH and Downward J: PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene. 30:3222–3233. 2011. View Article : Google Scholar : PubMed/NCBI

136 

Sanaei MJ, Razi S, Pourbagheri-Sigaroodi A and Bashash D: The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles. Transl Oncol. 18:1013642022. View Article : Google Scholar : PubMed/NCBI

137 

Papadimitrakopoulou VA, Soria JC, Jappe A, Jehl V, Klimovsky J and Johnson BE: Everolimus and erlotinib as second- or third-line therapy in patients with advanced non-small-cell lung cancer. J Thorac Oncol. 7:1594–1601. 2012. View Article : Google Scholar : PubMed/NCBI

138 

Ponticelli C: The pros and the cons of mTOR inhibitors in kidney transplantation. Expert Rev Clin Immunol. 10:295–305. 2015. View Article : Google Scholar

139 

Boers-Doets CB, Raber-Durlacher JE, Treister NS, Epstein JB, Arends AB, Wiersma DR, Lalla RV, Logan RM, van Erp NP and Gelderblom H: Mammalian target of rapamycin inhibitor-associated stomatitis. Future Oncol. 9:1883–1892. 2013. View Article : Google Scholar : PubMed/NCBI

140 

Gartrell BA, Ying J, Sivendran S, Boucher KM, Choueiri TK, Sonpavde G, Oh WK, Agarwal N and Galsky MD: Pulmonary complications with the use of mTOR inhibitors in targeted cancer therapy: A systematic review and meta-analysis. Target Oncol. 9:195–204. 2014. View Article : Google Scholar

141 

Gaumann A, Schlitt HJ and Geissler EK: Immunosuppression and tumor development in organ transplant recipients: The emerging dualistic role of rapamycin. Transpl Int. 21:207–217. 2008. View Article : Google Scholar

142 

El Hage A and Dormond O: Combining mtor inhibitors and T cell-based immunotherapies in cancer treatment. Cancers (Basel). 13:13592021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Pang X, Liu H, Long Y and Wang H: mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review). Int J Oncol 68: 21, 2026.
APA
Pang, X., Liu, H., Long, Y., & Wang, H. (2026). mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review). International Journal of Oncology, 68, 21. https://doi.org/10.3892/ijo.2025.5834
MLA
Pang, X., Liu, H., Long, Y., Wang, H."mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review)". International Journal of Oncology 68.2 (2026): 21.
Chicago
Pang, X., Liu, H., Long, Y., Wang, H."mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review)". International Journal of Oncology 68, no. 2 (2026): 21. https://doi.org/10.3892/ijo.2025.5834
Copy and paste a formatted citation
x
Spandidos Publications style
Pang X, Liu H, Long Y and Wang H: mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review). Int J Oncol 68: 21, 2026.
APA
Pang, X., Liu, H., Long, Y., & Wang, H. (2026). mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review). International Journal of Oncology, 68, 21. https://doi.org/10.3892/ijo.2025.5834
MLA
Pang, X., Liu, H., Long, Y., Wang, H."mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review)". International Journal of Oncology 68.2 (2026): 21.
Chicago
Pang, X., Liu, H., Long, Y., Wang, H."mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review)". International Journal of Oncology 68, no. 2 (2026): 21. https://doi.org/10.3892/ijo.2025.5834
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team