Mechanisms of Anticancer Agents Selective Against Drug-Resistant Leukemia
Drug resistance is a significant problem in cancer therapy, because it is a general phenomenon among all malignancies and there is no effective solution. Therefore, there is an unmet clinical need for new therapies targeting drug-resistant malignancies, which is challenging due to the limited knowledge about drug resistance mechanisms and the lack of appropriate cancer models and research tools. This group's long-term goal is to elucidate the mechanisms whereby cancer cells acquire resistance to treatment, and to rationally develop antitumor agents based on such knowledge that will effectively treat drug-resistant malignancies.
Research by this group has demonstrated the unique biological features of CXLs, particularly their potential to treat drug-resistant leukemias. Nevertheless, the precise mechanism that accounts for the distinctive anticancer profile of CXLs, including CXL’s cellular targets, has yet to be firmly established. During the course of preliminary studies, the group has developed two structurally similar CXLs as chemical probes and several pairs of leukemia cell lines as cancer models for mechanistic investigation. The main objectives of this project are to elucidate the mechanisms of action for CXLs by employing the unique chemical probes and cancer models we developed and to validate its anticancer potential in a clinically relevant engraftment model. The resulting knowledge is expected to rationalize the selective anticancer activity of CXLs towards drug-resistant leukemias and to establish the foundation for future translational development.
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A bibliography of this group’s published research is attached.