HER-3 targeting with an antibody-drug conjugate
Lucía Gandullo
Centro de Investigación del Cáncer (CIC-IBMCC, Universidad de Salamanca-CSIC)
In one out of every five cases of breast cancer, cells bear an excess of the HER2 protein due to gene amplification. Due to this overexpression, these tumors have been the target of specific anti-HER2 treatments, proven to be very effective in increasing survival rates. Such therapeutic options began with the approval for clinical use of trastuzumab in 2000 and continued with lapatinib, pertuzumab, trastuzumab-emtansine (T-DM1) and more recently neratinib, tucatinib and trastuzumab-deruxtecan. However, intrinsic and acquired resistance to such drugs is a clinical problem. Therefore, one of the biggest challenges that research in this field currently has is to design therapeutic strategies to attack such resistances.
Upregulation of HER3 is commonly observed in various malignancies, including breast cancer and has been linked to resistance to therapies targeting HER receptors. Taking all this under consideration, there is considerable effort to develop therapeutic methods to directly target HER3. Recently, we have described an anti-HER3 antibody-drug conjugate, EV20/MMAF, which exerted potent antitumoral properties against several models of primary and secondary resistance to trastuzumab, lapatinib, neratinib and T-DM1. In this talk, I will discuss our recent results in this project.