Mechanisms of Trastuzumab Resistance and Their Clinical Implications

Trastuzumab (Herceptin) is an excellent model of rationally designed targeted cancer treatment. However, less than 35% of patients with ErbB2-positive breast tumors respond to trastuzumab as a single agent, and 2-5% of trastuzumab-treated patients suffer from severe side effects, including cardiac dysfunction. Recent progress in understanding the mechanisms of trastuzumab antitumor function and cellular defects leading to trastuzumab resistance is summarized. Also explored is the potential of combination therapies for reversing trastuzumab resistance.