Therapeutic Opportunities For Anti-Met Antibody (Metmab) In Breast Cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The hepatocyte growth factor (HGF)/Met pathway drives cell proliferation, survival, migration and invasion, which are hallmarks of cancer. Animal models and microarray data suggest that elevated expression of Met is a poor prognostic factor in breast tumors. Our evaluation of primary breast tumors and cell lines has confirmed that expression of Met is found predominantly in the basal sub-type, which includes estrogen receptor (ER), progesterone receptor (PR) and HER2 triple negative (3N) tumors as well as some HER2+ basal tumors. In a panel of 3N basal breast tumors, 96% (25/26) of samples express Met by enzyme-linked immunosorbant assay (ELISA), with 42% (11/26) positive by immuno-histochemistry (IHC). All of the samples were positive for HGF as determined by ECLA, with 32% (8/25) of these primary tumors showing robust staining by IHC. To further explore the biological response of basal breast cancers to HGF, a panel of basal breast cancer cell lines were evaluated in cell proliferation, migration and invasion assays. While most lines tested showed a modest response to HGF in proliferation assays, the migratory and invasive response to HGF was more robust. Assessment of signaling pathways and gene signatures was also performed to better understand the nature of Met signaling leading to biological outcomes. HGF responsive lines were evaluated for growth in transgenic SCID mice expressing human HGF. MetMAb, a potent HGF-blocking Met monovalent monoclonal antibody, acts to inhibit HGF-driven effects in basal breast cancer cell lines in vitro and xenograft growth in vivo. Taken together, these data suggest that Met can drive invasive growth of basal breast tumors, and that treatment with MetMAb, alone or in combination with standard of care, may be therapeutically beneficial in these tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1203. doi:10.1158/1538-7445.AM2011-1203