Molecular targeted therapy of cancer has long been the focus of clinicians, with the human epidermal growth factor receptor-2 (HER2) signalling pathway being one of the most popular targets. However, in contrast to the plethora of anti-HER2 agents that have entered the breast cancer treatment paradigm, trastuzumab remains the only anti-HER2 drug that is approved for the first-line treatment of HER2 positive advanced gastric cancer. Recently, however, promising data are emerging with new anti-HER2 agents, including antibody-drug-conjugates (ADC) and bispecific antigens. In addition, also the combination of anti-HER2 therapy with immune checkpoint inhibition holds lots of promise for the treatment of HER2-positive stomach cancer. Despite being standard of care in the treatment of HER2-positive gastric cancer, the role of HER2 as a therapeutic target is far less established in other gastrointestinal malignancies. However, promising data with the ADC trastuzumab-deruxtecan are emerging in colorectal cancer and also in biliary tract cancer phase I studies start to point towards a potential role for HER2 targeting.
