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Human epidermal growth factor receptor 2 (HER2)

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Human epidermal growth factor receptor 2 (HER2)

What is HER2?

Human epidermal growth factor receptor 2 (HER2) is a protein that normally helps control cell growth and specialisation [1].

Why is it important?

If there is too much HER2 present it increases the rate at which the cancer cells multiply and their ability to move to other parts of the body [2].

What is the evidence?

HER2 has been found at high levels in many different types of cancers [3, 4]. It is generally accepted that high levels of the HER2 protein are found in approximately 30% of salivary duct carcinoma (SDC) cases [5, 6]. This high HER2 expression is significant because it is associated with aggressive behaviour, mirroring that of HER2-positive breast cancer [7, 8].

Is HER2 a potential target for new and existing treatments?

Specific HER2-targeted drugs (TDM1, trastuzumab, and pertuzumab) have been effective in treating HER2-positive Salivary Gland Carcinoma (SGC) that cannot be cured [9]. However, these HER2-directed therapies are not currently approved by regulators for use in SGC in the UK, Europe, or the US.

A Phase 1 trial (NCT04450732) for a targeted drug called GQ1001 has been completed on patients with different types of advanced cancers, including salivary gland cancer [10]. These cancers were all HER2 positive, meaning they expressed the HER2 protein. The trial found that GQ1001 produced encouraging results and did not cause severe side effects.

A Phase 2 trial (NCT03614364) enrolled patients with HER2-positive SDC and treated them with combination of chemotherapy and a HER2-targeted drug. The results were promising and showed that tumours shrank significantly and extended the lives of patients [11].

Useful resources

Read more about how to get your tumour profiled and add to a research biobank here:

References

  1. Olayioye MA. Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res. 2001; 3(6):385-9.
  2. Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer. 2001; 8(1):11-31.
  3. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985; 230(4730):1132-9.
  4. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007; 26(45):6469-87.
  5. Omar N, Yan B, Salto-Tellez M. HER2: An emerging biomarker in non-breast and non-gastric cancers. Pathogenesis. 2015; 2(3):1-9.
  6. Ferguson DC, Momeni Boroujeni A, Zheng T, Mohanty AS, Ho AL, Arcila ME, et al. ERBB2 amplification status in 67 salivary duct carcinomas assessed by immunohistochemistry, fluorescence in situ hybridization, and targeted exome sequencing. Mod Pathol. 2022; 35(7):895-902.
  7. Glisson B, Colevas AD, Haddad R, Krane J, El-Naggar A, Kies M, et al. HER2 Expression in Salivary Gland Carcinomas: Dependence on Histological Subtype. Clinical Cancer Research. 2004; 10(3):944-6.
  8. Press MF, Pike MC, Hung G, Zhou JY, Ma Y, George J, et al. Amplification and Overexpression of HER-2/neu in Carcinomas of the Salivary Gland: Correlation with Poor Prognosis1. Cancer Research. 1994; 54(21):5675-82.
  9. Haigh J, Patel K, Rack S, Jimenez-Labaig P, Betts G, Harrington K, et al. The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers. Current Oncology. 2024; 31:5652-61.
  10. Zhou C, Wang B, Teng C, Yang H, Piha-Paul SA, Richardson G, et al. A phase Ia study of a novel anti-HER2 antibody-drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors. J Transl Med. 2025; 23(1):37.
  11. Lee J, Park S, Jung HA, Lee SH, Seo S, Kim SB, et al. A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas. Cancer. 2023; 129(19):2966-74.

Last Updated December 2025