HER3 and its Ligand, Heregulin, as Targets for Cancer Therapy

Emerging evidence suggests that human epidermal growth factor receptor 3 plays a critical role in cell-survival and drug-resistance in cancer cells. Several kinds of agents targeting this receptor are currently progressing through preclinical or clinical investigations. These agents are usually monoclonal antibodies with unique characteristics, and some have shown efficacy and been welltolerated in clinical trials. For example, patritumab and seribantumab are thought to compete with ligand binding and have proven efficacy for some malignancies in Phase II clinical trials. LJM716 locks the human epidermal growth factor receptor 3 in the inactive conformation in both ligand-dependent and - independent cancers. Lumretuzumab is a glycoengineered antibody, which enhances antibody-dependent cell-mediated cytotoxicity. Duligotumab is an antibody that targets both the human epidermal growth factor receptors 1 and 3. Heregulin is a human epidermal growth factor receptor 3 ligand that represents an encouraging candidate biomarker for the prediction of the efficacy of agents targeting this receptor. Conclusion: A number of antibodies that interact with human epidermal growth factor receptors have been evaluated for clinical use. Ongoing clinical trials will address the remaining issues related to optimization of drug combination therapy and improving the targeting of each agent to the most appropriate individuals.