Trastuzumab represents the triumph of translational research. It is the only targeted agent currently used not only in metastatic setting but also in the adjuvant setting saving the lives of patients with HER2-positive early-stage breast cancer.
However, several questions, problems and challenges await solutions. Long-term complete clinical response rate is estimated to be less than 20% because of intrinsic or acquired resistance. Cardiotoxicity, timing, duration and best possible combination with empirical cytotoxic drugs and inefficacy to control brain metastases are further limitations.
Lapatinib, a small-molecule tyrosine kinase inhibitor of both the EGFR and HER2 provides exciting findings alone or in combination with trastuzumab and large-scale phase III clinical trials are underway.
This review articles discusses mechanisms of action and how limitations and hurdles would potentially be overcome for an optimal use trastuzumab, lapatinib, antiangioneic therapy (anti-VEGF) in combinations with modern chemotherapeutic regimens Furthermore, the development of biomarkers to predict response to targeted therapies, in a mean of personalized medicine, is highlighted.