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
March-2025 Volume 53 Issue 3

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
March-2025 Volume 53 Issue 3

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

Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma

  • Authors:
    • Xinyan Geng
    • Shirin Azarbarzin
    • Zejia Yang
    • Rena G. Lapidus
    • Xiaoxuan Fan
    • Yong Teng
    • Ranee Mehra
    • Kevin J. Cullen
    • Hancai Dan
  • View Affiliations / Copyright

    Affiliations: Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30332, USA
    Copyright: © Geng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 38
    |
    Published online on: January 27, 2025
       https://doi.org/10.3892/or.2025.8871
  • 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

The ErbB/HER family of protein‑tyrosine kinases and PI3K represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). A combination therapy of afatinib (ErbB inhibitor) and copanlisib (PI3K inhibitor), both Food and Drug Administration‑approved kinase inhibitors, can suppress the growth of human papillomavirus (HPV)‑positive HNSCC. The current study further evaluated the efficacy and clinical potential of this combination therapy for the treatment of HPV‑negative HNSCC in vitro and in vivo. Sulforhodamine B cell viability assay and Annexin V/propidium iodide staining demonstrated that this combination treatment markedly enhanced inhibition of cell viability and reduced cell survival when compared with treatment with either inhibitor alone in two HPV‑negative HNSCC cell lines. Notably, this combination also led to significant inhibition of xenograft tumor growth in mice, without any apparent effects on body weight. Western blot analysis found that copanlisib alone effectively blocked PI3K/Akt signaling but caused upregulation of HER2 and HER3 phosphorylation, as reported in other types of cancer. However, the combination of copanlisib and afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also increasing apoptosis. In conclusion, these results suggested that co‑targeting the ErbB family kinases and PI3K using a combination treatment of afatinib and copanlisib may have clinical potential for patients with HPV‑negative HNSCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

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. View Article : Google Scholar : PubMed/NCBI

2 

Powell SF, Vu L, Spanos WC and Pyeon D: The key differences between human papillomavirus-positive and -negative head and neck cancers: Biological and clinical implications. Cancers (Basel). 13:52062021. View Article : Google Scholar : PubMed/NCBI

3 

Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, Fabiánová E, Rudnai P and Brennan P: Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe. Am J Epidemiol. 165:814–820. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, Dal Maso LD, Daudt AW, Fabianova E, Fernandez L, et al: Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer epidemiology consortium. J Natl Cancer Inst. 99:777–789. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Zaryouh H, De Pauw I, Baysal H, Peeters M, Vermorken JB, Lardon F and Wouters A: Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR-targeting agents to treat head and neck squamous cell carcinoma. Med Res Rev. 42:112–155. 2022. View Article : Google Scholar : PubMed/NCBI

6 

Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE and Grandis JR: Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 6:922020. View Article : Google Scholar : PubMed/NCBI

7 

Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A and Gillison ML: Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 100:261–269. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Qin T, Li S, Henry LE, Liu S and Sartor MA: Molecular tumor subtypes of HPV-positive head and neck cancers: Biological characteristics and implications for clinical outcomes. Cancers (Basel). 13:27212021. View Article : Google Scholar : PubMed/NCBI

9 

Hennessey PT, Westra WH and Califano JA: Human papillomavirus and head and neck squamous cell carcinoma: Recent evidence and clinical implications. J Dent Res. 88:300–306. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Ferreira CC: The relation between human papillomavirus (HPV) and oropharyngeal cancer: A review. PeerJ. 11:e155682023. View Article : Google Scholar : PubMed/NCBI

11 

Tran NH, Sais D and Tran N: Advances in human papillomavirus detection and molecular understanding in head and neck cancers: Implications for clinical management. J Med Virol. 96:e297462024. View Article : Google Scholar : PubMed/NCBI

12 

Zumsteg ZS, Luu M, Yoshida EJ, Kim S, Tighiouart M, David JM, Shiao SL, Mita AC, Scher KS, Sherman EJ, et al: Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the national cancer data base. Cancer. 123:4583–4593. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Wen Y and Grandis JR: Emerging drugs for head and neck cancer. Expert Opin Emerg Drugs. 20:313–329. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Lee YS, Johnson DE and Grandis JR: An update: Emerging drugs to treat squamous cell carcinomas of the head and neck. Expert Opin Emerg Drugs. 23:283–299. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Perri F, Ionna F, Longo F, Della Vittoria Scarpati G, De Angelis C, Ottaiano A, Botti G and Caponigro F: Immune response against head and neck cancer: Biological mechanisms and implication on therapy. Transl Oncol. 13:262–274. 2020. View Article : Google Scholar : PubMed/NCBI

16 

Grandis JR and Tweardy DJ: Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 53:3579–3584. 1993.PubMed/NCBI

17 

Park BJ, Chiosea SI and Grandis JR: Molecular changes in the multistage pathogenesis of head and neck cancer. Cancer Biomark. 9:325–339. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Sharafinski ME, Ferris RL, Ferrone S and Grandis JR: Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck. 32:1412–1421. 2010. View Article : Google Scholar : PubMed/NCBI

19 

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

20 

Wee P and Wang Z: Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 9:522017. View Article : Google Scholar : PubMed/NCBI

21 

Alorabi M, Shonka NA and Ganti AK: EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: What is their current role? Crit Rev Oncol Hematol. 99:170–179. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Blaszczak W, Barczak W, Wegner A, Golusinski W and Suchorska WM: Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma. Med Oncol. 34:602017. View Article : Google Scholar : PubMed/NCBI

23 

Mehra R, Cohen RB and Burtness BA: The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol. 6:742–750. 2008.PubMed/NCBI

24 

Argiris A, Heron DE, Smith RP, Kim S, Gibson MK, Lai SY, Branstetter BF, Posluszny DM, Wang L, Seethala RR, et al: Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer. J Clin Oncol. 28:5294–5300. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Specenier P and Vermorken J: Afatinib in squamous cell carcinoma of the head and neck. Expert Opin Pharmacother. 17:1295–1301. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Machiels JPH, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, et al: Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): An open-label, randomised phase 3 trial. Lancet Oncol. 16:583–594. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Saddawi-Konefka R, Schokrpur S, Lui AJ and Gutkind JS: HER2 and HER3 as therapeutic targets in head and neck cancer. Cancer J. 28:339–345. 2022. View Article : Google Scholar : PubMed/NCBI

28 

Sacco AG and Worden FP: Molecularly targeted therapy for the treatment of head and neck cancer: A review of the ErbB family inhibitors. Onco Targets Ther. 9:1927–1943. 2016.PubMed/NCBI

29 

Rysman B, Mouawad F, Gros A, Lansiaux A, Chevalier D and Meignan S: Human epidermal growth factor receptor 3 in head and neck squamous cell carcinomas. Head Neck. 38 (Suppl 1):E2412–E2418. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Palumbo C, Benvenuto M, Focaccetti C, Albonici L, Cifaldi L, Rufini A, Nardozi D, Angiolini V, Bei A, Masuelli L and Bei R: Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma. Front Med (Lausanne). 10:10660212023. View Article : Google Scholar : PubMed/NCBI

31 

Kao HF, Liao BC, Huang YL, Huang HC, Chen CN, Chen TC, Hong YJ, Chan CY, Chia JS and Hong RL: Afatinib and pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (ALPHA Study): A phase II study with biomarker analysis. Clin Cancer Res. 28:1560–1571. 2022. View Article : Google Scholar : PubMed/NCBI

32 

Guo Y, Ahn MJ, Chan A, Wang CH, Kang JH, Kim SB, Bello M, Arora RS, Zhang Q, He X, et al: Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): An open-label, randomised phase III trial. Ann Oncol. 30:1831–1839. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Haddad R, Guigay J, Keilholz U, Clement PM, Fayette J, de Souza Viana L, Rolland F, Cupissol D, Geoffrois L, Kornek G, et al: Afatinib as second-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: Subgroup analyses of treatment adherence, safety and mode of afatinib administration in the LUX-Head and Neck 1 trial. Oral Oncol. 97:82–91. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Mellor P, Furber LA, Nyarko JNK and Anderson DH: Multiple roles for the p85α isoform in the regulation and function of PI3K signalling and receptor trafficking. Biochem J. 441:23–37. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert BR, et al: Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 3:761–769. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Cochicho D, Esteves S, Rito M, Silva F, Martins L, Montalvão P, Cunha M, Magalhães M, da Costa RMG and Felix A: PIK3CA gene mutations in HNSCC: Systematic review and correlations with HPV status and patient survival. Cancers (Basel). 14:12862022. View Article : Google Scholar : PubMed/NCBI

37 

Jung K, Kang H and Mehra R: Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC). Cancers Head Neck. 3:32018. View Article : Google Scholar : PubMed/NCBI

38 

García-Escudero R, Segrelles C, Dueñas M, Pombo M, Ballestín C, Alonso-Riaño M, Nenclares P, Álvarez-Rodríguez R, Sánchez-Aniceto G, Ruíz-Alonso A, et al: Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway. Oral Oncol. 79:55–63. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Cancer Genome Atlas Network, . Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 517:576–582. 2015. View Article : Google Scholar : PubMed/NCBI

40 

Marquard FE and Jücker M: PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer. Biochem Pharmacol. 172:1137292020. View Article : Google Scholar : PubMed/NCBI

41 

Poetsch M, Lorenz G and Kleist B: Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet. 132:20–24. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Sangale Z, Prass C, Carlson A, Tikishvili E, Degrado J, Lanchbury J and Stone S: A robust immunohistochemical assay for detecting PTEN expression in human tumors. Appl Immunohistochem Mol Morphol. 19:173–183. 2011. View Article : Google Scholar : PubMed/NCBI

43 

Squarize CH, Castilho RM, Abrahao AC, Molinolo A, Lingen MW and Gutkind JS: PTEN deficiency contributes to the development and progression of head and neck cancer. Neoplasia. 15:461–471. 2013. View Article : Google Scholar : PubMed/NCBI

44 

Psyrri A, Seiwert TY and Jimeno A: Molecular pathways in head and neck cancer: EGFR, PI3K, and more. Am Soc Clin Oncol Educ Book. 246–255. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Pezzuto F, Buonaguro L, Caponigro F, Ionna F, Starita N, Annunziata C, Buonaguro FM and Tornesello ML: Update on head and neck cancer: Current knowledge on epidemiology, risk factors, molecular features and novel therapies. Oncology. 89:125–136. 2015. View Article : Google Scholar : PubMed/NCBI

46 

Yang Z, Liao J, Schumaker L, Carter-Cooper B, Lapidus RG, Fan X, Gaykalova DA, Mehra R, Cullen KJ and Dan H: Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma. Oral Oncol. 131:1059392022. View Article : Google Scholar : PubMed/NCBI

47 

Yang Z, Liao J, Carter-Cooper BA, Lapidus RG, Cullen KJ and Dan H: Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway. BMC Cancer. 19:4852019. View Article : Google Scholar : PubMed/NCBI

48 

Packer LM, Geng X, Bonazzi VF, Ju RJ, Mahon CE, Cummings MC, Stephenson SA and Pollock PM: PI3K inhibitors synergize with FGFR inhibitors to enhance antitumor responses in FGFR2mutant endometrial cancers. Mol Cancer Ther. 16:637–648. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Chou TC: Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70:440–446. 2010. View Article : Google Scholar : PubMed/NCBI

50 

Chakrabarty A, Sánchez V, Kuba MG, Rinehart C and Arteaga CL: Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci USA. 109:2718–2723. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Meister KS, Godse NR, Khan NI, Hedberg ML, Kemp C, Kulkarni S, Alvarado D, LaVallee T, Kim S, Grandis JR and Duvvuri U: HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma. Sci Rep. 9:91302019. View Article : Google Scholar : PubMed/NCBI

52 

Young NR, Liu J, Pierce C, Wei TF, Grushko T, Olopade OI, Liu W, Shen C, Seiwert TY and Cohen EE: Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition. Mol Oncol. 7:359–368. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Cheng H, Yang X, Si H, Saleh AD, Xiao W, Coupar J, Gollin SM, Ferris RL, Issaeva N, Yarbrough WG, et al: Genomic and transcriptomic characterization links cell lines with aggressive head and neck cancers. Cell Rep. 25:1332–1345.e5. 2018. View Article : Google Scholar : PubMed/NCBI

54 

Zaryouh H, Van Loenhout J, Peeters M, Vermorken JB, Lardon F and Wouters A: Co-targeting the EGFR and PI3K/Akt pathway to overcome therapeutic resistance in head and neck squamous cell carcinoma: What about autophagy? Cancers (Basel). 14:61282022. View Article : Google Scholar : PubMed/NCBI

55 

Zaryouh H, De Pauw I, Baysal H, Pauwels P, Peeters M, Vermorken JB, Lardon F and Wouters A: The role of Akt in acquired cetuximab resistant head and neck squamous cell carcinoma: An in vitro study on a novel combination strategy. Front Oncol. 11:6979672021. View Article : Google Scholar : PubMed/NCBI

56 

Mock A, Plath M, Moratin J, Tapken MJ, Jäger D, Krauss J, Fröhling S, Hess J and Zaoui K: EGFR and PI3K pathway activities might guide drug repurposing in HPV-negative head and neck cancers. Front Oncol. 11:6789662021. View Article : Google Scholar : PubMed/NCBI

57 

Izumi H, Wang Z, Goto Y, Ando T, Wu X, Zhang X, Li H, Johnson DE, Grandis JR and Gutkind JS: Pathway-specific genome editing of PI3K/mTOR tumor suppressor genes reveals that PTEN loss contributes to cetuximab resistance in head and neck cancer. Mol Cancer Ther. 19:1562–1571. 2020. View Article : Google Scholar : PubMed/NCBI

58 

Martin D, Abba MC, Molinolo AA, Vitale-Cross L, Wang Z, Zaida M, Delic NC, Samuels Y, Lyons JG and Gutkind JS: The head and neck cancer cell oncogenome: A platform for the development of precision molecular therapies. Oncotarget. 5:8906–8923. 2014. View Article : Google Scholar : PubMed/NCBI

59 

van Harten AM, Poell JB, Buijze M, Brink A, Wells SI, René Leemans C, Wolthuis RMF and Brakenhoff RH: Characterization of a head and neck cancer-derived cell line panel confirms the distinct TP53-proficient copy number-silent subclass. Oral Oncol. 98:53–61. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Cook RS, Garrett JT, Sánchez V, Stanford JC, Young C, Chakrabarty A, Rinehart C, Zhang Y, Wu Y, Greenberger L, et al: ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis. Cancer Res. 71:3941–3951. 2011. View Article : Google Scholar : PubMed/NCBI

61 

Mishra R, Patel H, Alanazi S, Yuan L and Garrett JT: HER3 signaling and targeted therapy in cancer. Oncol Rev. 12:3552018.PubMed/NCBI

62 

Garrett JT, Sutton CR, Kurupi R, Bialucha CU, Ettenberg SA, Collins SD, Sheng Q, Wallweber J, Defazio-Eli L and Arteaga CL: Combination of antibody that inhibits ligand-independent HER3 dimerization and a p110α inhibitor potently blocks PI3K signaling and growth of HER2+ breast cancers. Cancer Res. 73:6013–6023. 2013. View Article : Google Scholar : PubMed/NCBI

63 

Milewska M, Cremona M, Morgan C, O'Shea J, Carr A, Vellanki SH, Hopkins AM, Toomey S, Madden SF, Hennessy BT and Eustace AJ: Development of a personalized therapeutic strategy for ERBB-gene-mutated cancers. Ther Adv Med Oncol. 10:17588340177460402018. View Article : Google Scholar : PubMed/NCBI

64 

Akbari Dilmaghani N, Safaroghli-Azar A, Pourbagheri-Sigaroodi A and Bashash D: The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies. IUBMB Life. 73:618–642. 2021. View Article : Google Scholar : PubMed/NCBI

65 

Nunnery SE and Mayer IA: Management of toxicity to isoform α-specific PI3K inhibitors. Ann Oncol. 30 (Suppl 10):x21–x26. 2019. View Article : Google Scholar

66 

Chia S, Gandhi S, Joy AA, Edwards S, Gorr M, Hopkins S, Kondejewski J, Ayoub JP, Califaretti N, Rayson D and Dent SF: Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer. Curr Oncol. 22:33–48. 2015. View Article : Google Scholar : PubMed/NCBI

67 

Suh KJ, Sung JH, Kim JW, Han SH, Lee HS, Min A, Kang MH, Kim JE, Kim JW, Kim SH, et al: EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release. Oncotarget. 8:63901–63910. 2017. View Article : Google Scholar : PubMed/NCBI

68 

Fiedler M, Schulz D, Piendl G, Brockhoff G, Eichberger J, Menevse AN, Beckhove P, Hautmann M, Reichert TE, Ettl T and Bauer RJ: Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines. Exp Cell Res. 396:1122592020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Geng X, Azarbarzin S, Yang Z, Lapidus RG, Fan X, Teng Y, Mehra R, Cullen KJ and Dan H: Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma. Oncol Rep 53: 38, 2025.
APA
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R.G., Fan, X., Teng, Y. ... Dan, H. (2025). Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma. Oncology Reports, 53, 38. https://doi.org/10.3892/or.2025.8871
MLA
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R. G., Fan, X., Teng, Y., Mehra, R., Cullen, K. J., Dan, H."Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma". Oncology Reports 53.3 (2025): 38.
Chicago
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R. G., Fan, X., Teng, Y., Mehra, R., Cullen, K. J., Dan, H."Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma". Oncology Reports 53, no. 3 (2025): 38. https://doi.org/10.3892/or.2025.8871
Copy and paste a formatted citation
x
Spandidos Publications style
Geng X, Azarbarzin S, Yang Z, Lapidus RG, Fan X, Teng Y, Mehra R, Cullen KJ and Dan H: Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma. Oncol Rep 53: 38, 2025.
APA
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R.G., Fan, X., Teng, Y. ... Dan, H. (2025). Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma. Oncology Reports, 53, 38. https://doi.org/10.3892/or.2025.8871
MLA
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R. G., Fan, X., Teng, Y., Mehra, R., Cullen, K. J., Dan, H."Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma". Oncology Reports 53.3 (2025): 38.
Chicago
Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R. G., Fan, X., Teng, Y., Mehra, R., Cullen, K. J., Dan, H."Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma". Oncology Reports 53, no. 3 (2025): 38. https://doi.org/10.3892/or.2025.8871
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