New approaches for the treatment of multidrug resistant cancer
Our overall aim is to develop new therapeutic approaches to overcome multidrug resistance (MDR) in cancer. Our earlier results indicate that the PEGylated liposomal formulation of doxorubicin (PLD) can significantly increase the survival in a genetically engineered mouse model of mammary cancer, suggesting that resistance conveyed by the MDR transporters may be overcome by the liposomal formulation of chemotherapeutic agents.
The goal of this project is to develop novel compounds, to optimize liposomal formulation strategies, and to characterize the formulated compounds using in vitro and in vivo models of therapy resistant cancer. Based on our preliminary results we will synthesize potent antitumor agents (anthracycline derivatives, MDR-selective compounds), and we will prepare sterically stabilized liposomes using PEG-lipids. We will test the free and formulated compounds in in vitro cytotoxicity assays in a panel of cancer cell lines. Compounds showing high potency will be evaluated in in vivo models of drug resistant cancer.
Gábor Mező, Zoltán Varga, Gergely Szakács