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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December-2020 Volume 44 Issue 6

Full Size Image

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
December-2020 Volume 44 Issue 6

Full Size Image

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer

  • Authors:
    • Tanzeel Khan
    • Alan M. Seddon
    • Angus G. Dalgleish
    • Said Khelwatty
    • Nikolaos Ioannou
    • Satvinder Mudan
    • Helmout Modjtahedi
  • View Affiliations / Copyright

    Affiliations: School of Life Science, Pharmacy and Chemistry, Kingston University London, Surrey KT1 2EE, UK, St George's Hospital, University of London, London SW17 0QT, UK, School of Cancer and Pharmaceutical Sciences, King's College London, London SE5 9NT, UK
    Copyright: © Khan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2581-2594
    |
    Published online on: October 22, 2020
       https://doi.org/10.3892/or.2020.7822
  • 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

Pancreatic cancer is one of the most aggressive, heterogeneous and fatal type of human cancers for which more effective therapeutic agents are urgently needed. Here, we investigated the sensitivity of a panel of seven human pancreatic cancer cell lines (HPCCLs) to treatment with various tyrosine kinase inhibitors (TKIs), cyclin‑dependent kinase (CDK) inhibitors, an inhibitor of STAT3 stattic, and a cytotoxic agent gemcitabine both as single agents and in combination. The membranous expression of various receptors and the effect of selected agents on cell cycle distribution, cell signaling pathways and migration was determined using flow cytometry, western blot analysis and scratch wound healing assays, respectively. While the expression of both HER‑3 and HER‑4 was low or negative, the expression of EGFR and HER2 was high or intermediate in all HPCCLs. Of all the agents examined, the CDK1/2/5/9 inhibitor, dinacicilib, was the most potent agent which inhibited the proliferation of all seven HPCCLs with IC50 values of ≤10 nM, followed by SRC targeting TKI dasatinib (IC50 of ≤258 nM), gemcitabine (IC50 of ≤330 nM), stattic (IC50 of ≤2 µM) and the irreversible pan‑HER TKI afatinib (IC50 of ≤2.95 µM). Treatment with afatinib and dasatinib inhibited the ligand‑induced phosphorylation of EGFR and SRC respectively. Statistically significant associations were found between HER2 expression and response to treatment with the ALK/IGF‑IR/InsR inhibitor ceritinib and fibroblast growth factor receptor (FGFR)1/2/3 inhibitor AZD4547, HER3 and IGF‑IR expression and their response to treatment with TKIs targeting HER family members (erlotinib and afatinib), and c‑MET and ALK7 expression and their response to treatment with stattic. Interestingly, treatment with a combination of afatinib with dasatinib and gemcitabine with dasatinib resulted in synergistic tumor growth inhibition in all HPCCLs examined. In contrast, the combination of afatinib with dinaciclib was found to be antagonistic. Finally, the treatment with afatinib, dasatinib and dinaciclib strongly inhibited the migration of all HPCCLs examined. In conclusion, the CDK1/2/5/9 inhibitor dinaciclib, irreversible pan‑HER TKI afatinib and SRC targeting TKI dasatinib were most effective at inhibiting the proliferation and migration of HPCCLs and the combination of afatinib with dasatinib and gemcitabine with dasatinib led to synergistic tumor growth inhibition in all HPCCLs examined. Our results support further investigation on the therapeutic potential of these combinations in future clinical trials in pancreatic cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Rawla P, Sunkara T and Gaduputi V: Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J Oncol. 10:10–27. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Carreras-Torres R, Johansson M, Gaborieau V, Haycock PC, Wade KH, Relton CL, Martin RM, Davey Smith G and Brennan P: The role of obesity, type 2 diabetes, and metabolic factors in pancreatic cancer: A mendelian randomization study. J Natl Cancer Inst. 109:djx0122017. View Article : Google Scholar

5 

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F and Straif K; International Agency for Research on Cancer Handbook Working Group, : Body Fatness and Cancer-Viewpoint of the IARC Working Group. N Engl J Med. 375:794–798. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK and Hruban RH: Recent progress in pancreatic cancer. CA Cancer J Clin. 63:318–348. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Ioannou N, Seddon AM, Dalgleish A, Mackintosh D and Modjtahedi H: Expression pattern and targeting of HER family members and IGF-IR in pancreatic cancer. Front Biosci (Landmark Ed). 2012(17): 2698–2724. 2012. View Article : Google Scholar

8 

Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK and Batra SK: Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 16:15–31. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Tebbutt N, Pedersen MW and Johns TG: Targeting the ERBB family in cancer: Couples therapy. Nat Rev Cancer. 13:663–673. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Li Q, Zhang L, Li X, Yan H, Yang L, Li Y, Li T, Wang J and Cao B: The prognostic significance of human epidermal growth factor receptor family protein expression in operable pancreatic cancer: HER1-4 protein expression and prognosis in pancreatic cancer. BMC Cancer. 16:9102016. View Article : Google Scholar : PubMed/NCBI

11 

Perini MV, Montagnini AL, Coudry R, Patzina R, Penteado S, Abdo EE, Diniz A, Jukemura J and da Cunha JE: Prognostic significance of epidermal growth factor receptor overexpression in pancreas cancer and nodal metastasis. ANZ J Surg. 85:174–178. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Mahipal A, Mcdonald MJ, Witkiewicz A and Carr BI: Cell membrane and cytoplasmic epidermal growth factor receptor expression in pancreatic ductal adenocarcinoma. Med Oncol. 29:134–139. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Einama T, Ueda S, Tsuda H, Ogasawara K, Hatsuse K, Matsubara O, Todo S and Yamamoto J: Membranous and cytoplasmic expression of epidermal growth factor receptor in metastatic pancreatic ductal adenocarcinoma. Exp Ther Med. 3:931–936. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, et al: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 25:1960–1966. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Ioannou N, Seddon AM, Dalgleish A, Mackintosh D and Modjtahedi H: Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC Cancer. 13:412013. View Article : Google Scholar : PubMed/NCBI

16 

Nones K, Waddell N, Song S, Patch AM, Miller D, Johns A, Wu J, Kassahn KS, Wood D, Bailey P, et al: Genome-wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT-ROBO, ITGA2 and MET signaling. Int J Cancer. 135:1110–1118. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Zhou W, Jubb AM, Lyle K, Xiao Q, Ong CC, Desai R, Fu L, Gnad F, Song Q, Haverty PM, et al: PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition. J Pathol. 234:502–513. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Zhu GH, Huang C, Qiu ZJ, Liu J, Zhang ZH, Zhao N, Feng ZZ and Lv XH: Expression and prognostic significance of CD151, c-Met, and integrin alpha3/alpha6 in pancreatic ductal adenocarcinoma. Dig Dis Sci. 56:1090–1098. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Liu C, Yang Z, Li D, Liu Z, Miao X, Yang L, Zou Q and Yuan Y: Overexpression of B2M and loss of ALK7 expression are associated with invasion, metastasis, and poor-prognosis of the pancreatic ductal adenocarcinoma. Cancer Biomark. 15:735–743. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Shields DJ, Murphy EA, Desgrosellier JS, Mielgo A, Lau SK, Barnes LA, Lesperance J, Huang M, Schmedt C, Tarin D, et al: Oncogenic Ras/Src cooperativity in pancreatic neoplasia. Oncogene. 30:2123–2134. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Nagaraj NS, Smith JJ, Revetta F, Washington MK and Merchant NB: Targeted inhibition of SRC kinase signaling attenuates pancreatic tumorigenesis. Mol Cancer Ther. 9:2322–2332. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Morton JP, Karim SA, Graham K, Timpson P, Jamieson N, Athineos D, Doyle B, McKay C, Heung MY, Oien KA, et al: Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology. 139:292–303. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Chee CE, Krishnamurthi S, Nock CJ, Meropol NJ, Gibbons J, Fu P, Bokar J, Teston L, O'Brien T, Gudena V, et al: Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas. Oncologist. 18:1091–1092. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Cros J, Raffenne J, Couvelard A and Poté N: Tumor heterogeneity in pancreatic adenocarcinoma. Pathobiology. 85:64–71. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Yao W, Maitra A and Ying H: Recent insights into the biology of pancreatic cancer. EBioMedicine. 53:1026552020. View Article : Google Scholar : PubMed/NCBI

26 

Haeberle L, Steiger K, Schlitter AM, Safi SA, Knoefel WT, Erkan M and Esposito I: Stromal heterogeneity in pancreatic cancer and chronic pancreatitis. Pancreatology. May 12–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

27 

Ioannou N, Dalgleish AG, Seddon AM, Mackintosh D, Guertler U, Solca F and Modjtahedi H: Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells. Br J Cancer. 105:1554–1562. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Stanley A, Ashrafi GH, Seddon AM and Modjtahedi H: Synergistic effects of various Her inhibitors in combination with IGF-1R, C-MET and Src targeting agents in breast cancer cell lines. Sci Rep. 7:39642017. View Article : Google Scholar : PubMed/NCBI

29 

Cunningham MP, Thomas H, Fan Z and Modjtahedi H: Responses of human colorectal tumor cells to treatment with the anti-epidermal growth factor receptor monoclonal antibody ICR62 used alone and in combination with the EGFR tyrosine kinase inhibitor gefitinib. Cancer Res. 66:7708–7715. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Ioannou N, Seddon AM, Dalgleish A, Mackintosh D, Solca F and Modjtahedi H: Acquired resistance of pancreatic cancer cells to treatment with gemcitabine and HER-inhibitors is accompanied by increased sensitivity to STAT3 inhibition. Int J Oncol. 48:908–918. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM and Matrisian LM: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74:2913–2921. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Adel N: Current treatment landscape and emerging therapies for pancreatic cancer. Am J Manag Care. 25 (1 Suppl):S3–S10. 2019.PubMed/NCBI

33 

Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, Seghezzi W, Paruch K, Dwyer MP, Doll R, et al: Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 9:2344–2353. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Nemunaitis JJ, Small KA, Kirschmeier P, Zhang D, Zhu Y, Jou YM, Statkevich P, Yao SL and Bannerji R: A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies. J Transl Med. 11:2592013. View Article : Google Scholar : PubMed/NCBI

35 

Frolov A, Schuller K, Tzeng CW, Cannon EE, Ku BC, Howard JH, Vickers SM, Heslin MJ, Buchsbaum DJ and Arnoletti JP: ErbB3 expression and dimerization with EGFR influence pancreatic cancer cell sensitivity to erlotinib. Cancer Biol Ther. 6:548–554. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Buck E, Eyzaguirre A, Haley JD, Gibson NW, Cagnoni P and Iwata KK: Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity. Mol Cancer Ther. 5:2051–2059. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Ware KE, Marshall ME, Heasley LR, Marek L, Hinz TK, Hercule P, Helfrich BA, Doebele RC and Heasley LE: Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression. PLoS One. 5:e141172010. View Article : Google Scholar : PubMed/NCBI

38 

Azuma K, Kawahara A, Sonoda K, Nakashima K, Tashiro K, Watari K, Izumi H, Kage M, Kuwano M, Ono M and Hoshino T: FGFR1 activation is an escape mechanism in human lung cancer cells resistant to afatinib, a pan-EGFR family kinase inhibitor. Oncotarget. 5:5908–5919. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Urtasun N, Vidal-Pla A, Pérez-Torras S and Mazo A: Human pancreatic cancer stem cells are sensitive to dual inhibition of IGF-IR and ErbB receptors. BMC Cancer. 15:2232015. View Article : Google Scholar : PubMed/NCBI

40 

Al-U'datt DGF, Al-Husein BAA and Qasaimeh GR: A mini-review of c-Met as a potential therapeutic target in melanoma. Biomed Pharmacother. 88:194–202. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Bian C, Liu Z, Li D and Zhen L: PI3K/AKT inhibition induces compensatory activation of the MET/STAT3 pathway in non-small cell lung cancer. Oncol Lett. 15:9655–9662. 2018.PubMed/NCBI

42 

Rahimi N, Hung W, Tremblay E, Saulnier R and Elliott B: c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells. J Biol Chem. 273:33714–33721. 1998. View Article : Google Scholar : PubMed/NCBI

43 

Xue C, Tian Y, Zhang J, Zhao Y, Zhan J, Fang W and Zhang L: In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma. Drug Des Devel Ther. 10:1299–1306. 2016.PubMed/NCBI

44 

Garcia-Reyes B, Kretz AL, Ruff JP, von Karstedt S, Hillenbrand A, Knippschild U, Henne-Bruns D and Lemke J: The emerging role of cyclin-dependent kinases (CDKs) in pancreatic ductal adenocarcinoma. Int J Mol Sci. 19:32192018. View Article : Google Scholar

45 

Miao X, Koch G, Ait-Oudhia S, Straubinger RM and Jusko WJ: Pharmacodynamic modeling of cell cycle effects for gemcitabine and trabectedin combinations in pancreatic cancer cells. Front Pharmacol. 7:4212016. View Article : Google Scholar : PubMed/NCBI

46 

Duong HQ, Yi YW, Kang HJ, Bae I, Jang YJ, Kwak SJ and Seong YS: Combination of dasatinib and gemcitabine reduces the ALDH1A1 expression and the proliferation of gemcitabine-resistant pancreatic cancer MIA PaCa-2 cells. Int J Oncol. 44:2132–2138. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Ma L, Wei J, Su GH and Lin J: Dasatinib can enhance paclitaxel and gemcitabine inhibitory activity in human pancreatic cancer cells. Cancer Biol Ther. 20:855–865. 2019. View Article : Google Scholar : PubMed/NCBI

48 

Hong DS, Choe JH, Naing A, Wheler JJ, Falchook GS, Piha-Paul S, Moulder SL, George GC, Choe JM, Strauss LC, et al: A phase 1 study of gemcitabine combined with dasatinib in patients with advanced solid tumors. Invest New Drugs. 31:918–926. 2013. View Article : Google Scholar : PubMed/NCBI

49 

Evans TRJ, Van Cutsem E, Moore MJ, Bazin IS, Rosemurgy A, Bodoky G, Deplanque G, Harrison M, Melichar B, Pezet D, et al: Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer. Ann Oncol. 28:354–361. 2017. View Article : Google Scholar : PubMed/NCBI

50 

Cardin DB, Goff LW, Chan E, Whisenant JG, Dan Ayers G, Takebe N, Arlinghaus LR, Yankeelov TE, Berlin J and Merchant N: Dual Src and EGFR inhibition in combination with gemcitabine in advanced pancreatic cancer: Phase I results: A phase I clinical trial. Invest New Drugs. 36:442–450. 2018. View Article : Google Scholar : PubMed/NCBI

51 

Nagaraj NS, Washington MK and Merchant NB: Combined blockade of Src kinase and epidermal growth factor receptor with gemcitabine overcomes STAT3-mediated resistance of inhibition of pancreatic tumor growth. Clin Cancer Res. 17:483–493. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Khan T, Seddon AM, Dalgleish AG, Khelwatty S, Ioannou N, Mudan S and Modjtahedi H: Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer. Oncol Rep 44: 2581-2594, 2020.
APA
Khan, T., Seddon, A.M., Dalgleish, A.G., Khelwatty, S., Ioannou, N., Mudan, S., & Modjtahedi, H. (2020). Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer. Oncology Reports, 44, 2581-2594. https://doi.org/10.3892/or.2020.7822
MLA
Khan, T., Seddon, A. M., Dalgleish, A. G., Khelwatty, S., Ioannou, N., Mudan, S., Modjtahedi, H."Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer". Oncology Reports 44.6 (2020): 2581-2594.
Chicago
Khan, T., Seddon, A. M., Dalgleish, A. G., Khelwatty, S., Ioannou, N., Mudan, S., Modjtahedi, H."Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer". Oncology Reports 44, no. 6 (2020): 2581-2594. https://doi.org/10.3892/or.2020.7822
Copy and paste a formatted citation
x
Spandidos Publications style
Khan T, Seddon AM, Dalgleish AG, Khelwatty S, Ioannou N, Mudan S and Modjtahedi H: Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer. Oncol Rep 44: 2581-2594, 2020.
APA
Khan, T., Seddon, A.M., Dalgleish, A.G., Khelwatty, S., Ioannou, N., Mudan, S., & Modjtahedi, H. (2020). Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer. Oncology Reports, 44, 2581-2594. https://doi.org/10.3892/or.2020.7822
MLA
Khan, T., Seddon, A. M., Dalgleish, A. G., Khelwatty, S., Ioannou, N., Mudan, S., Modjtahedi, H."Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer". Oncology Reports 44.6 (2020): 2581-2594.
Chicago
Khan, T., Seddon, A. M., Dalgleish, A. G., Khelwatty, S., Ioannou, N., Mudan, S., Modjtahedi, H."Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: Implications for future clinical trials in pancreatic cancer". Oncology Reports 44, no. 6 (2020): 2581-2594. https://doi.org/10.3892/or.2020.7822
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