Targeting Notch signaling cross-talk with estrogen receptor and ErbB-2 in breast cancer.

In ERα-positive and HER2/neu overexpressing tumors, Notch signaling is partially suppressed and its role is limited by the overwhelming proliferative and survival effects of ERα-dependent and ErbB-2-dependent pathways. In triple-negative cancers, on the other hand, Notch signaling becomes a key mediator of proliferation, survival and possibly invasion. Our data (Rizzo et al., 2008a) and recent data by the Altieri group (Lee et al., 2008) support the hypothesis that triple-negative breast cancers are heavily dependent on Notch signaling, and thus the Notch pathway is a promising therapeutic target in this breast cancer subtype.