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
March-2018 Volume 52 Issue 3

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
March-2018 Volume 52 Issue 3

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
Article

Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells

  • Authors:
    • Kyu Sic You
    • Yong Weon Yi
    • Sahng-June Kwak
    • Yeon-Sun Seong
  • View Affiliations / Copyright

    Affiliations: Graduate School of Convergence Medical Science, Dankook University, Cheonan 31116, Republic of Korea, ExoCoBio Inc, Seoul 08594, Republic of Korea, Department of Biochemistry, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
  • Pages: 828-840
    |
    Published online on: January 15, 2018
       https://doi.org/10.3892/ijo.2018.4244
  • 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

Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth factor signaling and resistance to inhibitors for epidermal growth factor receptor (EGFR), despite the overexpression of EGFR protein, and this is associated with a malignant behavior and a poor prognosis. In this study, to elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify inhibitors that exert a synergistic effect with EGFR inhibition, we examined the inhibitory effects of selected protein kinase inhibitors (PKIs) in combination with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC cell line. MK‑2206, an AKT inhibitor, and a group of mammalian target of rapamycin (mTOR) inhibitors were found to exert synergistic lethal effects in combination with gefitinib in MDA‑MB‑231 cells. The combination of gefitinib/MK‑2206 exerted a prominent synergistic lethal effect in an MTT cell viability assay and a growth inhibitory effect in a long-term colony-forming assay in 2 MSL subtype TNBC cell lines (MDA‑MB‑231 and HS578T) and one basal-like (BL) subtype TNBC cell line (MDA‑MB-468). Gefitinib/MK‑2206 treatment synergistically decreased the mTOR signaling target substrates along with the downregulation of ribosomal protein S6 (RPS6), a marker of cell proliferation and target substrate of the AKT-mTOR signaling pathway. In addition, gefitinib markedly reduced the viability of MDA‑MD‑231 and HS578T cells when regulatory-associated protein of mTOR (RPTOR) was suppressed by siRNA-based knockdown (KD). These results thus suggest that RPTOR mediates, at least partially, the resistance to EGFR inhibition in TNBC cells. Therefore, targeting the mTOR complex 1 (mTORC1) pathway may be a potential strategy for the treatment of EGFR-resistant TNBC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Mohamed A, Krajewski K, Cakar B and Ma CX: Targeted therapy for breast cancer. Am J Pathol. 183:1096–1112. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Brenton JD, Carey LA, Ahmed AA and Caldas C: Molecular classification and molecular forecasting of breast cancer: Ready for clinical application? J Clin Oncol. 23:7350–7360. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, Schwartz GF, Park PK, Rosenberg AL, Brill K, et al: Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: A single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer. 110:876–884. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Podo F, Buydens LM, Degani H, Hilhorst R, Klipp E, Gribbestad IS, Van Huffel S, van Laarhoven HW, Luts J, Monleon D, et al FEMME Consortium: Triple-negative breast cancer: Present challenges and new perspectives. Mol Oncol. 4:209–229. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Lehmann BD and Pietenpol JA: Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J Pathol. 232:142–150. 2014. View Article : Google Scholar :

7 

Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, et al: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 26:1275–1281. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C, Fralick M, Kumar R and Clemons M: Survival outcomes for patients with metastatic triple-negative breast cancer: Implications for clinical practice and trial design. Clin Breast Cancer. 9:29–33. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Costa R, Shah AN, Santa-Maria CA, Cruz MR, Mahalingam D, Carneiro BA, Chae YK, Cristofanilli M, Gradishar WJ and Giles FJ: Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development. Cancer Treat Rev. 53:111–119. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P and Narod SA: Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Eccles SA: The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. Int J Dev Biol. 55:685–696. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Wheeler DL, Dunn EF and Harari PM: Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol. 7:493–507. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Yarden Y and Pines G: The ERBB network: At last, cancer therapy meets systems biology. Nat Rev Cancer. 12:553–563. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Reis-Filho JS and Tutt AN: Triple negative tumours: A critical review. Histopathology. 52:108–118. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT and Perou CM: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 19:264–271. 2006. View Article : Google Scholar

16 

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 10:5367–5374. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Nakai K, Hung MC and Yamaguchi H: A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res. 6:1609–1623. 2016.PubMed/NCBI

18 

Reis-Filho JS, Milanezi F, Carvalho S, Simpson PT, Steele D, Savage K, Lambros MB, Pereira EM, Nesland JM, Lakhani SR, et al: Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: Immunohistochemical and chromogenic in situ hybridization analysis. Breast Cancer Res. 7:R1028–R1035. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Reis-Filho JS, Pinheiro C, Lambros MB, Milanezi F, Carvalho S, Savage K, Simpson PT, Jones C, Swift S, Mackay A, et al: EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J Pathol. 209:445–453. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Yarden Y and Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2:127–137. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Burness ML, Grushko TA and Olopade OI: Epidermal growth factor receptor in triple-negative and basal-like breast cancer: Promising clinical target or only a marker? Cancer J. 16:23–32. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Alvarez RH, Valero V and Hortobagyi GN: Emerging targeted therapies for breast cancer. J Clin Oncol. 28:3366–3379. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Yi YW, Hong W, Kang HJ, Kim HJ, Zhao W, Wang A, Seong YS and Bae I: Inhibition of the PI3K/AKT pathway potentiates cytotoxicity of EGFR kinase inhibitors in triple-negative breast cancer cells. J Cell Mol Med. 17:648–656. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Jin Q and Esteva FJ: Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia. 13:485–498. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Karamouzis MV, Konstantinopoulos PA and Papavassiliou AG: Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. Lancet Oncol. 10:709–717. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Liu P, Cheng H, Roberts TM and Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 8:627–644. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Nahta R, Yu D, Hung MC, Hortobagyi GN and Esteva FJ: Mechanisms of disease: Understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 3:269–280. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Yamaguchi H, Chang SS, Hsu JL and Hung MC: Signaling crosstalk in the resistance to HER family receptor targeted therapy. Oncogene. 33:1073–1081. 2014. View Article : Google Scholar

29 

Baselga J: Targeting tyrosine kinases in cancer: The second wave. Science. 312:1175–1178. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Yi YW, You K, Bae EJ, Kwak SJ, Seong YS and Bae I: Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6. Int J Oncol. 47:122–132. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Massihnia D, Galvano A, Fanale D, Perez A, Castiglia M, Incorvaia L, Listì A, Rizzo S, Cicero G, Bazan V, et al: Triple negative breast cancer: Shedding light onto the role of pi3k/akt/mtor pathway. Oncotarget. 7:60712–60722. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Goldstein D, Bushmeyer SM, Witt PL, Jordan VC and Borden EC: Effects of type I and II interferons on cultured human breast cells: Interaction with estrogen receptors and with tamoxifen. Cancer Res. 49:2698–2702. 1989.PubMed/NCBI

33 

Duong HQ, You KS, Oh S, Kwak SJ and Seong YS: Silencing of NRF2 reduces the expression of ALDH1A1 and ALDH3A1 and sensitizes to 5-FU in pancreatic cancer cells. Antioxidants. 6:62017. View Article : Google Scholar

34 

Kim SI, Kim HJ, Lee HJ, Lee K, Hong D, Lim H, Cho K, Jung N and Yi YW: Application of a non-hazardous vital dye for cell counting with automated cell counters. Anal Biochem. 492:8–12. 2016. View Article : Google Scholar

35 

Biscardi JS, Ishizawar RC, Silva CM and Parsons SJ: Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res. 2:203–210. 2000. View Article : Google Scholar

36 

Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N and Slamon DJ: Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/'triple-negative' breast cancer cell lines growing in vitro. Breast Cancer Res Treat. 105:319–326. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Feder D and Bishop JM: Purification and enzymatic characterization of pp60c-src from human platelets. J Biol Chem. 265:8205–8211. 1990.PubMed/NCBI

38 

Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM and Abraham RT: A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 60:3504–3513. 2000.

39 

Kovacina KS, Park GY, Bae SS, Guzzetta AW, Schaefer E, Birnbaum MJ and Roth RA: Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem. 278:10189–10194. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, Aebersold R and Sonenberg N: Regulation of 4E-BP1 phosphorylation: A novel two-step mechanism. Genes Dev. 13:1422–1437. 1999. View Article : Google Scholar : PubMed/NCBI

41 

Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr and Kinzler KW: Cancer genome landscapes. Science. 339:1546–1558. 2013. View Article : Google Scholar : PubMed/NCBI

42 

Wullschleger S, Loewith R and Hall MN: TOR signaling in growth and metabolism. Cell. 124:471–484. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Laplante M and Sabatini DM: mTOR signaling at a glance. J Cell Sci. 122:3589–3594. 2009. View Article : Google Scholar : PubMed/NCBI

44 

Sabatini DM: mTOR and cancer: Insights into a complex relationship. Nat Rev Cancer. 6:729–734. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Ueng SH, Chen SC, Chang YS, Hsueh S, Lin YC, Chien HP, Lo YF, Shen SC and Hsueh C: Phosphorylated mTOR expression correlates with poor outcome in early-stage triple negative breast carcinomas. Int J Clin Exp Pathol. 5:806–813. 2012.PubMed/NCBI

46 

Walsh S, Flanagan L, Quinn C, Evoy D, McDermott EW, Pierce A and Duffy MJ: mTOR in breast cancer: Differential expression in triple-negative and non-triple-negative tumors. Breast. 21:178–182. 2012. View Article : Google Scholar

47 

Montero JC, Esparís-Ogando A, Re-Louhau MF, Seoane S, Abad M, Calero R, Ocaña A and Pandiella A: Active kinase profiling, genetic and pharmacological data define mTOR as an important common target in triple-negative breast cancer. Oncogene. 33:148–156. 2014. View Article : Google Scholar

48 

Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, Pritchard K, Eisen A, Vandenberg T, Taylor M, et al: Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol. 27:4536–4541. 2009. View Article : Google Scholar : PubMed/NCBI

49 

Jovanović B, Mayer IA, Mayer EL, Abramson VG, Bardia A, Sanders ME, Kuba MG, Estrada MV, Beeler JS, Shaver TM, et al: A Randomized phase II neoadjuvant study of cisplatin, paclitaxel with or without everolimus in patients with stage II/III triple-negative breast cancer (TNBC): Responses and long-term outcome correlated with increased frequency of DNA damage response gene mutations, TNBC subtype, AR status, and Ki67. Clin Cancer Res. 23:4035–4045. 2017. View Article : Google Scholar

50 

Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, et al: Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer. Ann Oncol. 25:1122–1127. 2014. View Article : Google Scholar : PubMed/NCBI

51 

Oualla K, El-Zawahry HM, Arun B, Reuben JM, Woodward WA, Gamal El-Din H, Lim B, Mellas N, Ueno NT and Fouad TM: Novel therapeutic strategies in the treatment of triple-negative breast cancer. Ther Adv Med Oncol. 9:493–511. 2017. View Article : Google Scholar : PubMed/NCBI

52 

Liu T, Yacoub R, Taliaferro-Smith LD, Sun SY, Graham TR, Dolan R, Lobo C, Tighiouart M, Yang L, Adams A, et al: Combinatorial effects of lapatinib and rapamycin in triple-negative breast cancer cells. Mol Cancer Ther. 10:1460–1469. 2011. View Article : Google Scholar : PubMed/NCBI

53 

Madden JM, Mueller KL, Bollig-Fischer A, Stemmer P, Mattingly RR and Boerner JL: Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer. Breast Cancer Res Treat. 147:283–293. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P and Sabatini DM: mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 110:163–175. 2002. View Article : Google Scholar : PubMed/NCBI

55 

Chen B, Tan Z, Gao J, Wu W, Liu L, Jin W, Cao Y, Zhao S, Zhang W, Qiu Z, et al: Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer. J Exp Clin Cancer Res. 34:1262015. View Article : Google Scholar : PubMed/NCBI

56 

Iwenofu OH, Lackman RD, Staddon AP, Goodwin DG, Haupt HM and Brooks JS: Phospho-S6 ribosomal protein: A potential new predictive sarcoma marker for targeted mTOR therapy. Mod Pathol. 21:231–237. 2008. View Article : Google Scholar

57 

Komori Y, Yada K, Ohta M, Uchida H, Iwashita Y, Fukuzawa K, Kashima K, Yokoyama S, Inomata M and Kitano S: Mammalian target of rapamycin signaling activation patterns in pancreatic neuroendocrine tumors. J Hepatobiliary Pancreat Sci. 21:288–295. 2014. View Article : Google Scholar

58 

Masuda M, Chen WY, Miyanaga A, Nakamura Y, Kawasaki K, Sakuma T, Ono M, Chen CL, Honda K and Yamada T: Alternative mammalian target of rapamycin (mTOR) signal activation in sorafenib-resistant hepatocellular carcinoma cells revealed by array-based pathway profiling. Mol Cell Proteomics. 13:1429–1438. 2014. View Article : Google Scholar : PubMed/NCBI

59 

Knoll M, Macher-Goeppinger S, Kopitz J, Duensing S, Pahernik S, Hohenfellner M, Schirmacher P and Roth W: The ribosomal protein S6 in renal cell carcinoma: Functional relevance and potential as biomarker. Oncotarget. 7:418–432. 2016. View Article : Google Scholar :

60 

Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, Logie A, Hargreaves J, Hickinson DM, Wilkinson RW, et al: Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol. 3:248–261. 2009. View Article : Google Scholar : PubMed/NCBI

61 

Maira SM, Stauffer F, Brueggen J, Furet P, Schnell CC, Brachmann S, Chène P, De Pover A, Schoemaker K, et al: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 7:1851–1863. 2008. View Article : Google Scholar : PubMed/NCBI

62 

Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, Oyarzabal J, Pastor J, Bischoff JR and Fernandez-Capetillo O: A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol. 18:721–727. 2011. View Article : Google Scholar : PubMed/NCBI

63 

O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MW, et al: In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 65:4500–4505. 2005. View Article : Google Scholar : PubMed/NCBI

64 

Shah NP, Lee FY, Luo R, Jiang Y, Donker M and Akin C: Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 108:286–291. 2006. View Article : Google Scholar : PubMed/NCBI

65 

Rivera VM, Squillace RM, Miller D, Berk L, Wardwell SD, Ning Y, Pollock R, Narasimhan NI, Iuliucci JD, Wang F, et al: Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens. Mol Cancer Ther. 10:1059–1071. 2011. View Article : Google Scholar : PubMed/NCBI

66 

Chun KH, Kosmeder JW II, Sun S, Pezzuto JM, Lotan R, Hong WK and Lee HY: Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J Natl Cancer Inst. 95:291–302. 2003. View Article : Google Scholar : PubMed/NCBI

67 

Schuler W, Sedrani R, Cottens S, Häberlin B, Schulz M, Schuurman HJ, Zenke G, Zerwes HG and Schreier MH: SDZ RAD, a new rapamycin derivative: Pharmacological properties in vitro and in vivo. Transplantation. 64:36–42. 1997. View Article : Google Scholar : PubMed/NCBI

68 

Flanagan WM, Corthésy B, Bram RJ and Crabtree GR: Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 352:803–807. 1991. View Article : Google Scholar : PubMed/NCBI

69 

Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA, et al: The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 51:5522–5532. 2008. View Article : Google Scholar : PubMed/NCBI

70 

Carnero A: Novel inhibitors of the PI3K family. Expert Opin Investig Drugs. 18:1265–1277. 2009. View Article : Google Scholar : PubMed/NCBI

71 

Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B, et al: A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 125:733–747. 2006. View Article : Google Scholar : PubMed/NCBI

72 

García-Martínez JM, Moran J, Clarke RG, Gray A, Cosulich SC, Chresta CM and Alessi DR: Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem J. 421:29–42. 2009. View Article : Google Scholar : PubMed/NCBI

73 

Vlahos CJ, Matter WF, Hui KY and Brown RF: A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 269:5241–5248. 1994.PubMed/NCBI

74 

Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS, et al: MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. 9:1956–1967. 2010. View Article : Google Scholar : PubMed/NCBI

75 

Gills JJ and Dennis PA: Perifosine: Update on a novel Akt inhibitor. Curr Oncol Rep. 11:102–110. 2009. View Article : Google Scholar : PubMed/NCBI

76 

Nghiem P, Pearson G and Langley RG: Tacrolimus and pimecrolimus: From clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol. 46:228–241. 2002. View Article : Google Scholar : PubMed/NCBI

77 

Edwards SR and Wandless TJ: The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain. J Biol Chem. 282:13395–13401. 2007. View Article : Google Scholar : PubMed/NCBI

78 

Shor B, Zhang WG, Toral-Barza L, Lucas J, Abraham RT, Gibbons JJ and Yu K: A new pharmacologic action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis. Cancer Res. 68:2934–2943. 2008. View Article : Google Scholar : PubMed/NCBI

79 

Marone R, Cmiljanovic V, Giese B and Wymann MP: Targeting phosphoinositide 3-kinase: Moving towards therapy. Biochim Biophys Acta. 1784:159–185. 2008. View Article : Google Scholar

80 

Somwar R, Niu W, Kim DY, Sweeney G, Randhawa VK, Huang C, Ramlal T and Klip A: Differential effects of phosphatidylinositol 3-kinase inhibition on intracellular signals regulating GLUT4 translocation and glucose transport. J Biol Chem. 276:46079–46087. 2001. View Article : Google Scholar : PubMed/NCBI

81 

Yu K, Toral-Barza L, Shi C, Zhang WG, Lucas J, Shor B, Kim J, Verheijen J, Curran K, Malwitz DJ, et al: Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 69:6232–6240. 2009. View Article : Google Scholar : PubMed/NCBI

82 

Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H, Hirono S, Yamazaki K and Yamori T: Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst. 98:545–556. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
You KS, Yi YW, Kwak S and Seong Y: Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells. Int J Oncol 52: 828-840, 2018.
APA
You, K.S., Yi, Y.W., Kwak, S., & Seong, Y. (2018). Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells. International Journal of Oncology, 52, 828-840. https://doi.org/10.3892/ijo.2018.4244
MLA
You, K. S., Yi, Y. W., Kwak, S., Seong, Y."Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells". International Journal of Oncology 52.3 (2018): 828-840.
Chicago
You, K. S., Yi, Y. W., Kwak, S., Seong, Y."Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells". International Journal of Oncology 52, no. 3 (2018): 828-840. https://doi.org/10.3892/ijo.2018.4244
Copy and paste a formatted citation
x
Spandidos Publications style
You KS, Yi YW, Kwak S and Seong Y: Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells. Int J Oncol 52: 828-840, 2018.
APA
You, K.S., Yi, Y.W., Kwak, S., & Seong, Y. (2018). Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells. International Journal of Oncology, 52, 828-840. https://doi.org/10.3892/ijo.2018.4244
MLA
You, K. S., Yi, Y. W., Kwak, S., Seong, Y."Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells". International Journal of Oncology 52.3 (2018): 828-840.
Chicago
You, K. S., Yi, Y. W., Kwak, S., Seong, Y."Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells". International Journal of Oncology 52, no. 3 (2018): 828-840. https://doi.org/10.3892/ijo.2018.4244
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