ICE Bioscience Posters

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The DNA damage response (DDR) encompasses a series of cellular processes that detect and repair genomic lesions. Targeting DDR pathways and inhibiting DNA repair mechanisms have emerged as promising strategies in cancer therapy, and significant progress has been made in the discovery of DDR-related inhibitors. However, drug resistance has become an increasingly prevalent challenge in this field. To better understand compound potency across various cancer cell lines, we generated drug-sensitive and drug-resistant cell lines by knocking out key DDR genes (e.g., BRCA1/2, XRCC1) and culturing cells under selective pressure from PARP inhibitors. Additionally, together with wild-type (WT) cells commonly used in DDR-related drug discovery, we established a DDR cell panel encompassing 14 distinct cancer types. This panel has been rigorously validated through in vitro proliferation assays and in vivo efficacy studies. Furthermore, sequencing and bioinformatic analyses have been employed to elucidate the mechanisms underlying drug sensitivity and resistance. Our findings demonstrate that this DDR cell panel offers a rapid and comprehensive platform for evaluating DDR inhibitors, thereby facilitating the efficient discovery of novel therapeutics in cancer treatment.