Thymine DNA Glycosylase as a Novel Target for Lung Cancer

The purpose of this research is to develop novel therapeutics for lung cancer LC based on targeting the dual DNA repair and epigenetic factor Thymine DNA Glycosylase TDG. In principle, inhibiting TDG may both disrupt DNA repair and the cancer epigenetic state of LC cells, thus achieving a therapeutic effect that enhances the actions of existing chemotherapies and is complementary to current epigenetic therapy agents.In the current reporting period, we showed that TDG knockdown in the non-small lung cancer NSLC cell lines A549 and NCI H1993 causes cell cycle alteration and reduction of clonogenic capacity. In order to pursue mechanistic studies of this anti-cancer effect, we have generated derivatives of these LC cell lines that express doxycycline-inducible shTDG constructs. In preparation of future experiments with anonymized patient-derived cell lines and mouse xenograft experiments, we have submitted the relevant HRPO and ACURO forms, respectively.