“Self-inhibition of HER2 at fever temperatures may prevent dimerization with HER3”

Background HER2 receptor is overexpressed in different aggressive and recurrent tumors, and the modulation of its conformational changes has been achieved using immunotherapy or chemotherapy. Objective To assess the role of fever temperatures on the dynamics of HER2 in the absence of a binding partner. Methods Molecular dynamics simulations of apo-HER2 were performed at 37□-40□, in order to gauge its intramolecular dynamics. Results HER2 assumes an inactive and “bent” conformation at 40□, while it maintains its extended, active conformation that can dimerize with other HER partners, in the 37□-39□ range. Conclusion These novel results indicate the role of fever temperatures on modulating conformational changes in an essential tumor target. Cancer treatment can leverage the use of thermal therapy at particular fever points, in order to complement existing radio or chemotherapy options.