Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer.

Abstract

The introduction of HER2-targeted therapy for breast and gastric patients with <i>ERBB2</i> (<i>HER2</i>) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, with four approved in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next-generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved. We have recognized that <i>HER2</i> amplification is not limited to breast and gastric cancer but is also found in a variety of tumor types such as colon cancer, bladder cancer, and biliary cancer. Furthermore, HER2-targeted therapy has signal of activity in several tumor types. In addition to <i>HER2</i> amplification and overexpression, there is also increased recognition of activating <i>HER2</i> mutations and their potential therapeutic relevance. Furthermore, there is a rapidly growing number of new therapeutics targeting HER2 including small-molecule inhibitors, antibody-drug conjugates, and bispecific antibodies. Taken together, an increasing number of patients are likely to benefit from approved and emerging HER2-targeted therapies.