HER2remmers

HER2remmers are targeted therapies that inhibit signaling driven by the human epidermal growth factor receptor 2 (HER2). HER2 amplification or overexpression occurs in a subset of breast cancers and in gastric or gastroesophageal junction cancers, among others, and is associated with more aggressive disease. By interfering with HER2 signaling, these agents slow tumor growth and, in many cases, improve clinical outcomes.

Therapies in this class are grouped into three main types: monoclonal antibodies (e.g., trastuzumab, pertuzumab, margetuximab) that bind to HER2 on the cell surface; tyrosine kinase inhibitors (e.g., lapatinib, neratinib, tucatinib) that block the intracellular kinase activity of HER2; and antibody-drug conjugates (e.g., ado-trastuzumab emtansine, fam-trastuzumab deruxtecan) that deliver cytotoxic drugs directly to HER2-expressing cells. Some regimens combine multiple agents to enhance activity or overcome resistance.

Clinical use varies by tumor type and stage. In breast cancer, HER2remmers are integral to treatment for HER2-positive disease in the adjuvant, neoadjuvant, and metastatic settings; regimens include combinations such as trastuzumab and pertuzumab with a taxane, and ado-trastuzumab emtansine for residual disease or metastatic disease. In gastric and gastroesophageal junction cancers, trastuzumab and, more recently, other HER2-directed therapies are used in appropriate cases. TKIs are often employed in metastatic disease and some adjuvant contexts.

Adverse effects depend on the agent but commonly include cardiotoxicity with trastuzumab-containing regimens, diarrhea with neratinib, and interstitial lung disease risk with some antibody-drug conjugates. Cardiac monitoring and selection of agents based on comorbidity are standard practice.