Title:HER3 and its Ligand, Heregulin, as Targets for Cancer Therapy
Volume: 11
Issue: 3
Author(s): Hisato Kawakami and Kimio Yonesaka
Affiliation:
Keywords:
EGFR, HER3, heregulin, LJM716, lumretuzumab, non-small cell lung cancer, patritumab, seribantumab (Alphabetically
arranged).
Abstract: 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.
