A new study shows how SRC, a nonmembrane tyrosine kinase, is a common signaling node in trastuzumab resistance caused by different mechanisms in HER2-positive breast cancers (pages 461–469). A SRC inhibitor restored trastuzumab sensitivity in vitro and in mouse tumor models, suggesting a new way to tackle drug resistance in breast tumors.

Human epidermal growth factor receptor-2 (HER2) is one of the most dominant oncogenes in breast cancer. It is overexpressed in approximately 20% of human breast cancers and is associated with poor clinical prognosis and patient survival 1. HER2 belongs to a family of four receptors including HER1, HER3 and HER4 that activates downstream signaling pathways by forming both homo-and heterodimers 2. A monoclonal antibody that binds to the juxtamembrane domain of HER2, trastuzumab, was the first anti-HER2 treatment that was approved by the US Food and Drug Administration for clinical use for people with HER2-positive breast cancer 3. Individuals with metastatic, HER2-positive breast cancer treated with trastuzumab as an adjuvant and in combination with chemotherapy show significant clinical benefit 3, 4.