Survival of HER2-Positive Breast Cancer Cells: Receptor Signaling to Apoptotic Control Centers

Abstract

HER2 is overexpressed in a subset of breast cancers and controls an oncogenic signaling network that inhibits tumor cell death through the specific biochemical regulation of apoptotic pathways. In particular, the mitochondrial pathway for apoptosis is important for death induced by inhibitors of HER2. This review focuses on the connections between this oncogenic signaling network and individual components of the mitochondrial pathway. A comprehensive view of this signaling network is crucial for developing novel drugs in this area and to gain an understanding of how these regulatory interactions are altered in drug-refractory cancers.

Keywords: AKT; BAD; BCL-2; lapatinib; mTOR; trastuzumab.

Figure 1.

Interface between the HER2 signaling network and apoptotic control centers. HER2 activates 2 major signaling pathways (ERK and AKT) that utilize transcriptional and posttranscriptional mechanisms to inhibit the mitochondrial pathway of apoptosis. The network dynamics are illustrated before the addition of lapatinib (A) and after the addition of the drug (B). These interactions are supported by the literature, but the true complexity of this interface is likely much greater.