HER2 Receptor — Cell Growth Protein and Biomarker

Human epidermal growth factor receptor 2 (HER2), encoded by the ERBB2 gene, is a transmembrane receptor tyrosine kinase belonging to the EGFR family. In physiological states, HER2 participates in complex signalling cascades that mediate cell proliferation, survival, and differentiation. It lacks a direct ligand-binding domain, instead activating downstream pathways such as PI3K/Akt and MAPK through heterodimerisation with other ligand-bound ERBB family members.

In some tumours, amplification of the ERBB2 gene leads to marked overexpression of the HER2 protein on the cell surface. This constitutive activation triggers unchecked cellular proliferation, resistance to apoptosis, and increased angiogenesis, defining an aggressive disease subtype known clinically as HER2-positive cancer.

Testing for HER2 status is an essential initial step in staging and treatment planning for relevant tumours. Historically, HER2-positive cancers were associated with poorer outcomes because of their rapid growth rate. Today, the presence of HER2 overexpression alters the entire therapeutic strategy. It allows oncologists to recommend powerful targeted therapies that selectively attack HER2-bearing cells while sparing healthy tissue lacking the receptor, significantly improving progression-free and overall survival rates.

HER2 status is evaluated on tumour tissue obtained via biopsy or surgery. The initial test is usually immunohistochemistry (IHC), which scores the intensity of HER2 protein staining from 0 (negative) to 3+ (positive). A score of 2+ is considered equivocal and requires reflex testing using in situ hybridisation methods, such as fluorescent in situ hybridisation (FISH), to verify whether the ERBB2 gene itself is amplified within the tumour cell nuclei.

HER2 testing is standard clinical practice in breast cancer, where roughly 15 to 20 percent of cases are HER2-positive. It is also routinely evaluated in gastroesophageal adenocarcinoma, including stomach cancer and tumours of the gastroesophageal junction. Clinicians are increasingly examining HER2 status in select cases of colorectal cancer, non-small cell lung cancer, salivary gland carcinomas, and biliary tract malignancies.

Confirmation of HER2 positivity opens access to targeted therapies. Monoclonal antibodies like trastuzumab and pertuzumab bind the outer portion of the receptor, halting signalling and marking cells for immune destruction. Antibody-drug conjugates deliver cytotoxic agents directly into HER2-expressing cells. Small-molecule tyrosine kinase inhibitors (such as tucatinib or lapatinib) block signalling from inside the cell. Emerging therapies also benefit patients classified as 'HER2-low'.