Potential new therapeutic target for a subset of breast cancers

The main cause of death in women with breast cancer is spread of the original tumor to distant sites, a process known as metastasis. New therapeutic targets are urgently needed. A team of researchers led by Stefan Offermanns and Thomas Worzfeld, at the Max-Planck-Institute for Heart and Lung Research, Germany, has now generated data in mice and humans that suggest that the protein Plexin-B1 represents a new candidate therapeutic target to treat patients with breast cancer found to overexpress the molecule ErbB-2. ErbB-2 is overexpressed in approximately 30% of all breast cancers, and ErbB-2-overexpressing tumors have high metastatic potential and poor prognosis. Offermanns, Worzfeld, and colleagues found that overexpression of ErbB-2 in human breast cancer cell lines led to activation of Plexin-B1, and that this promoted human breast cancer cells to develop in vitro characteristics of metastatic cells. Moreover, in a mouse model of ErbB-2-overexpressing breast cancer, ablation of Plexin-B1 reduced the occurrence of metastases, while in human patients with ErbB-2-overexpressing breast cancer, low levels of Plexin-B1 expression correlated with better prognosis. Offermanns, Worzfeld, and colleagues therefore suggest that blocking the ErbB-2/Plexin-B1 interaction or inhibiting Plexin-B1-mediated signaling might reduce the risk of metastasis in patients with breast cancer overexpressing ErbB-2.