Relevance of EGFR-HER2 Dual Inhibition in Breast Cancer

The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are key members of the receptor tyrosine kinase family. Under normal physiological conditions, they play crucial roles in regulating cellular homeostasis and development, including cell differentiation, proliferation, and survival. However, when dysregulated due to mutation, amplification, or overexpression, these receptors become potent drivers of tumorigenesis, especially in breast cancer (BC). BC, being the second most prevalent cancer globally, remains a major contributor to female mortality. The EGFR and HER2 overexpression are present in nearly 15–30% of all BC cases and are a hallmark of aggressive BC and drug resistance, correlating with poor prognosis. Over the years, multiple tyrosine kinase inhibitors (TKIs) have been developed, showing promising responses against previously limited treatment options. This review focuses on strategies for designing dual EGFR-HER2 inhibitors for the treatment of BC and on insights into the development of new dual inhibitors.