ICE Bioscience Posters

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DNA damage is a major threat to cell survival. Not properly repaired DNA damage can lead to cell senescence, apoptosis or tumor development. DDR (DNA Damage Repair) is a collection of bioprocesses which cells utilize in order to identify and correct the DNA damage of the genome. The usage of various compounds for targeting DNA damage responses as well as attenuating DNA repair is also an approach for cancer therapy that has been widely studied in recent years. Despite the success of drug discovery of DDR related inhibitor, drug resistance has become an emerging issue of the field. Here we have constructed multiple cancer cell lines which are either DDR gene, such as XRCC1 and FANCD2, knock-out or resistant to certain DDR inhibitors. Together with the corresponding parental cell lines, we have generated a DDR cell panel which covers 12 different cancer types. We have first validated those DDR inhibitor sensitive or resistant cell lines with functional cell proliferation assays. Additionally, RNAseq has been performed for all constructed resistant cell lines. In combination with a thorough bioinformatic analysis using our in-house generated algorithms, we can provide the genetic background information of the resistant cell lines and top features that potentially contribute to the resistance mechanism. The representative data in this study has shown that LINC02709, BDKRB1, and PRKCQ are the top featured genes in A375 Vemurafenib resistant cell. Meanwhile, cell cycle, ECM-receptor interaction, and DNA replication are the most enriched KEGG terms. Lastly, we have validated this cell panel against multiple inhibitors targeting different DDR vital proteins such as ATM, PARP, POLQ etc. The result has shown that our unique DDR cell panel is capable of providing fast and comprehensive evaluation of DDR related inhibitors, thus facilitate faster and more efficient discovery of DDR inhibitors in the cancer therapy field.