Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance

Overview

Journal Mol Cancer Ther

Date 2019 Nov 3

PMID 31676542

Citations 16

Authors

Nabil F Saba

Zhuo Gerogia Chen

Missak Haigentz

Paolo Bossi

Alessandra Rinaldo

Juan P Rodrigo

Antti A Makitie

Robert P Takes

Primoz Strojan

Jan B Vermorken

Alfio Ferlito

Affiliations

Soon will be listed here.

Abstract

Despite the recent approval of immune-modulatory agents, EGFR inhibition continues to be a cornerstone in the management of squamous cell carcinoma of the head and neck (SCCHN) namely in combination with radiotherapy in the treatment of locoregionally advanced disease as well as in platinum-sensitive recurrent or metastatic disease in the first-line setting. Importantly, recent evidence has emerged supporting also an immune-modulatory effect of EGFR inhibition, and interest has now focused on utilizing these effects in the current treatment approaches for SCCHN. In this report, we review the rationale and evidence supporting the forging of this new alliance in optimizing the treatment of SCCHN.

Citing Articles

Surface Functionalization of Nanocarriers with Anti-EGFR Ligands for Cancer Active Targeting.

Spada A, Gerber-Lemaire S Nanomaterials (Basel). 2025; 15(3).

PMID: 39940134 PMC: 11820047. DOI: 10.3390/nano15030158.

Modulating tumor-associated macrophages through CSF1R inhibition: a potential therapeutic strategy for HNSCC.

Chen K, Li X, Dong S, Guo Y, Luo Z, Zhuang S J Transl Med. 2025; 23(1):27.

PMID: 39780232 PMC: 11707955. DOI: 10.1186/s12967-024-06036-3.

Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.

Gauss C, Stone L, Ghafouri M, Quan D, Johnson J, Fribley A Cells. 2024; 13(12.

PMID: 38920648 PMC: 11201455. DOI: 10.3390/cells13121018.

Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck.

Tanaka H, Enokida T, Okano S, Fujisawa T, Tanaka N, Takeshita N Front Oncol. 2023; 13:1221352.

PMID: 38074688 PMC: 10703151. DOI: 10.3389/fonc.2023.1221352.

New insights into RAS in head and neck cancer.

Jagadeeshan S, Novoplansky O, Cohen O, Kurth I, Hess J, Rosenberg A Biochim Biophys Acta Rev Cancer. 2023; 1878(6):188963.

PMID: 37619805 PMC: 11815531. DOI: 10.1016/j.bbcan.2023.188963.

References

Zandberg D, Strome S . The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 2014; 50(7):627-32. DOI: 10.1016/j.oraloncology.2014.04.003. View

Yarden Y, Sliwkowski M . Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001; 2(2):127-37. DOI: 10.1038/35052073. View

Licitra L, Storkel S, Kerr K, Van Cutsem E, Pirker R, Hirsch F . Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2012; 49(6):1161-8. DOI: 10.1016/j.ejca.2012.11.018. View

Lu Y, Li X, Liang K, Luwor R, Siddik Z, Mills G . Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab. Cancer Res. 2007; 67(17):8240-7. DOI: 10.1158/0008-5472.CAN-07-0589. View

Cohen E, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn M . Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2018; 393(10167):156-167. DOI: 10.1016/S0140-6736(18)31999-8. View

Schneider-Merck T, Lammerts van Bueren J, Berger S, Rossen K, van Berkel P, Derer S . Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J Immunol. 2009; 184(1):512-20. DOI: 10.4049/jimmunol.0900847. View

Huang S, Bock J, Harari P . Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res. 1999; 59(8):1935-40. View

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-1867. PMC: 5564292. DOI: 10.1056/NEJMoa1602252. View

Li C, Iida M, Dunn E, Ghia A, Wheeler D . Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene. 2009; 28(43):3801-13. PMC: 2900381. DOI: 10.1038/onc.2009.234. View

10.

Olayioye M, Neve R, Lane H, Hynes N . The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000; 19(13):3159-67. PMC: 313958. DOI: 10.1093/emboj/19.13.3159. View

11.

Kawamoto T, Sato J, Le A, Polikoff J, Sato G, Mendelsohn J . Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci U S A. 1983; 80(5):1337-41. PMC: 393592. DOI: 10.1073/pnas.80.5.1337. View

12.

Shames D, Carbon J, Walter K, Jubb A, Kozlowski C, Januario T . High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck. PLoS One. 2013; 8(2):e56765. PMC: 3586092. DOI: 10.1371/journal.pone.0056765. View

13.

Jiang N, Wang D, Hu Z, Shin H, Qian G, Rahman M . Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma. Mol Cancer Ther. 2014; 13(7):1826-36. PMC: 4090261. DOI: 10.1158/1535-7163.MCT-13-1093. View

14.

Boeckx C, Baay M, Wouters A, Specenier P, Vermorken J, Peeters M . Anti-epidermal growth factor receptor therapy in head and neck squamous cell carcinoma: focus on potential molecular mechanisms of drug resistance. Oncologist. 2013; 18(7):850-64. PMC: 3720640. DOI: 10.1634/theoncologist.2013-0013. View

15.

Masui H, Kawamoto T, Sato J, Wolf B, Sato G, Mendelsohn J . Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 1984; 44(3):1002-7. View

16.

Lee J, Soung Y, Kim S, Nam H, Park W, Nam S . Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2005; 11(8):2879-82. DOI: 10.1158/1078-0432.CCR-04-2029. View

17.

Andre P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T . Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell. 2018; 175(7):1731-1743.e13. PMC: 6292840. DOI: 10.1016/j.cell.2018.10.014. View

18.

Bossi P, Bergamini C, Siano M, Cossu Rocca M, Sponghini A, Favales F . Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab. Clin Cancer Res. 2016; 22(15):3961-70. DOI: 10.1158/1078-0432.CCR-15-2547. View

19.

Hynes N, Lane H . ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005; 5(5):341-54. DOI: 10.1038/nrc1609. View

20.

Swanson M, Sinha U . Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer—review of current data. Oral Oncol. 2014; 51(1):12-5. DOI: 10.1016/j.oraloncology.2014.10.010. View