HER dimerization, or receptor pairing, is a critical driver of tumor growth. The HER family is composed of 4 receptors that must dimerize in order to activate downstream signaling. Dimerization leads to the phosphorylation of the intracellular domains of the paired receptors, resulting in activation of cell proliferation and survival pathways.1
HER2 is the ideal receptor for HER dimerization. Although all receptors in the HER family are capable of dimerizing, receptors preferentially dimerize with HER2 because it is in an "open" conformation.2 Because HER2 is continually ready to dimerize, when HER2 is overexpressed, it promotes the formation of HER2 dimers.3 HER2-containing dimers are also thought to have increased signaling potency relative to those without HER2.2
Preclinical studies suggest that the HER2:HER3 dimer is the most potent oncogenic HER pair because it activates 2 important pathways involved in tumorigenesis.4 HER2 activates the MAPK cell proliferation pathway, and HER3 activates the PI3K cell survival pathway.5 The HER2:HER3 dimer may play a crucial role in the aggressive tumor growth seen in malignancies driven by HER2 overexpression.5
Genentech is dedicated to researching the potential benefits of inhibition of HER2 dimerization and its possible role in the future of personalized medicine for HER2+ breast cancer patients.
ResearchHDIs is a central source for medical professionals, students, and basic and translational researchers to learn more about the importance of HER receptors, dimerization, and their relationship to cancer.