The Notch pathway is a well-established mediator of cell-cell communication that plays a critical role in stem cell survival, self-renewal, cell fate decisions,
tumorigenesis, invasion,
metastasis, and drug resistance in a variety of
cancers. An interesting form of crosstalk exists between the
Notch receptor and the
Epidermal Growth Factor Receptor Tyrosine Kinase family, which consists of HER-1, -2, -3, and -4. Overexpression of HER and/or Notch occurs in several human
cancers including brain, lung, breast, ovary, and skin making them potent oncogenes capable of advancing malignant disease. Continued assessment of interplay between these two critical signaling networks uncovers new insight into mechanisms used by HER-driven
cancer cells to exploit Notch as a compensatory pathway. The compensatory Notch pathway maintains HER-induced downstream signals transmitted to pathways such as
Mitogen Activated Protein Kinase and
Phosphatidylinositol 3-Kinase (PI3K), thereby allowing
cancer cells to survive
molecular targeted therapies, undergo epithelial to mesenchymal transitioning, and increase cellular invasion. Uncovering the critical crosstalk between the HER and Notch pathways can lead to improved screening for the expression of these oncogenes enabling patients to optimize their personal treatment options and predict potential treatment resistance. This review will focus on the current state of crosstalk between the HER and
Notch receptors and the effectiveness of current
therapies targeting HER-driven
cancers.