Most epithelial ovarian cancer (OC) patients are diagnosed with advanced-stage disease and develop tumour drug resistance resulting in a high reoccurrence rate and high death rate. Our preliminary data show that a specific inhibitor of histone deacetylase (HDAC) reverses response in OC cells resistant to carboplatin (CBP).
DYRK1B signalling network could be a key branch of mammalian DNA damage response that coordinates double-strand repair on transcribed chromatin. With these in mind, this joint proposal will examine the role of HDAC and DYRK1B in reducing drug resistance. Then we will develop magnetic nanoparticles with low Curie temperature, which can be employed to self-regulate the hyperthermia temperature. Finally, we will develop core-shell structured nano drug carrier with magnetic nanoparticles as the core and thermal response hydrogel as the shell which will contain anti-cancer drug and inhibitor, TSA (HDAC inhibitor) and/or AZ191 (DYRK1B inhibitor). Alternating magnetic field-induced heat will trigger the release of the drug and inhibitor due to the increase of temperature. It is expected that both the inhibitor and magnetic induction hyperthermia will improve the sensitivity of chemotherapy. As a result, the synergistic effect of multimodal therapy of cancer, including hyperthermia, chemotherapy and molecular targeted therapy, can be achieved. Through the implementation of this project, it is hoped that the international cooperation between the scientists of Croatia and China can be strengthened and young scientists can be trained.