Identification of head and neck cancers (SCCHN) that may respond to dual inhibition of EGFR and HER3 signaling.

5575 Background: Oncogenic signaling through the epidermal growth factor receptor family is one of the most frequent alterations found in human epithelial cancers. These receptor tyrosine kinases mediate their effects via high-level co-expression and homo- and heterodimerization events that drive tumor growth, metastasis, and survival. Extensive preclinical studies suggested that some cell lines depend on oncogenic autocrine signaling through HER3 (Wilson et al.). This phenotype was particularly prominent in cell lines derived from SCCHN and was strongly correlated with high HRG expression. Interestingly, two patients with SCCHN tumors that expressed high levels of HRG in our phase Ia trial (abstract #95245) of MEHD7954A, a dual-action human IgG1 antibody that blocks ligand binding to EGFR and HER3 (Schaefer et al.) had partial responses. To further explore the hypothesis that high-level HRG expression defines a sub-population of SCCHN that may be sensitive to agents targeting HER3, and to identify other ...