Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Cancer

Epidermal growth factor receptor 3 (EGFR3; HER3; ErbB3); HER2 (EGFR2; ErbB2; neu)

Patient sample and mouse studies identified oncogenic somatic mutations in ERBB3 that could guide the use of HER2 and ErbB3 inhibitors. Whole-exome sequencing of 507 human primary tumor samples identified protein-altering somatic mutations in ERBB3 in 12% of gastric cancers, 11% of colon cancers and sporadically in other types of cancer. In both mouse and human cell lines, ERBB3 mutations plus ErbB2 expression promoted oncogenic transformation, anchorage-independent growth and IL-3-independent cell survival. In a mouse model for Erbb3 mutant leukemia, anti-ErbB3 mAbs or the anti-HER2 mAb Herceptin trastuzumab decreased disease severity and increased survival compared with a control mAb. Next steps include conducting studies to further elucidate the mechanisms by which mutant ERBB3 drives oncogenesis.
Roche's Genentech Inc. unit markets Herceptin to treat breast and gastric cancers (see Driving cancer through ErbB3, page 1).

SciBX 6(22); doi:10.1038/scibx.2013.539
Published online June 6, 2013

Patent and licensing status undisclosed

Jaiswal, B.S. et al. Cancer Cell; published online May 13, 2013;
doi:10.1016/j.ccr.2013.04.012
Contact: Somasekar Seshagiri, Genentech Inc., South San Francisco, Calif.
e-mail:
sekar@gene.com