antiHER2

Anti-HER2 refers to therapies that target the HER2 receptor (also known as ERBB2), a member of the human epidermal growth factor receptor family. HER2 is overexpressed or amplified in a subset of cancers, most notably breast cancer and gastroesophageal adenocarcinoma. By blocking HER2 signaling or delivering cytotoxic payloads to HER2-expressing cells, anti-HER2 treatments aim to reduce tumor growth and improve survival.

Therapies include monoclonal antibodies such as trastuzumab and pertuzumab, antibody-drug conjugates such as ado-trastuzumab emtansine and trastuzumab deruxtecan, and small molecule tyrosine kinase inhibitors such as lapatinib, neratinib, and tucatinib. Some regimens combine two HER2-targeted agents to achieve dual blockade, often with chemotherapy.

HER2 status is determined by immunohistochemistry and/or in situ hybridization. In breast cancer, anti-HER2 therapy is standard for tumors that overexpress HER2, used in neoadjuvant, adjuvant, and metastatic settings; dual anti-HER2 therapy with trastuzumab and pertuzumab is common in early-stage disease. In gastric or gastroesophageal junction cancer, trastuzumab is added to chemotherapy for HER2-positive tumors.

Cardiotoxicity is a notable risk with trastuzumab and other HER2-directed antibodies, requiring cardiac monitoring. Tyrosine kinase inhibitors can cause diarrhea, rash, and liver toxicity; some antibody-drug conjugates carry risks such as interstitial lung disease. Side effects vary by agent.

Resistance to anti-HER2 therapy may be intrinsic or acquired, related to downstream pathway activation or HER2 alterations. Ongoing research examines strategies to overcome resistance, CNS activity with certain agents, and combinations with immunotherapies.