Investigation of drug resistance dynamics in cetuximab-resistant NCI-H508 and oxaliplatin-resistant SW480 colorectal cancer cell lines under continuous and intermittent drug treatment using cellular dna barcoding technology

Date

2025-8-27

Author

Başar, Öykü Yağmur

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Despite significant advancements in colorectal cancer treatment, the emergence of drug resistance remains a significant challenge to effective therapeutic outcomes. Anti-cancer drug treatments exert selective pressure on tumor cell populations, enabling the survival and expansion of resistant clones. Previous studies have shown that different drug treatment regimens can impose distinct evolutionary pressures, shaping the drug resistance process. This thesis aimed to investigate the dynamics of acquired therapy resistance in colorectal cancer cell lines under either intermittent or continuous treatment regimens. Cellular DNA Barcoding technology was employed to uncover the clonal dynamics throughout the resistance process. Oxaliplatin resistant barcoded SW480 and cetuximab-resistant barcoded NCI-H508 cell populations were established under both treatment regimens as models of drug resistance. Clonal behavior in both treatment groups of the NCI-H508 and SW480 resistant populations was assessed using amplicon sequencing followed by barcode analysis, with barcodes classified as “Sensitive”, “Pre-existing”, or “De Novo” based on their growth dynamics. Subsequently, secondary drug screenings were conducted using a 50-compound drug library consisting of commonly used colorectal cancer therapeutics to identify potential therapeutic vulnerabilities of the drug-resistant SW480 and NCI-H508 populations. Overall, this study aimed to explore treatment regimen–based clonal dynamics of drug resistance and to identify potential therapeutic opportunities, with the ultimate goal of guiding more effective treatment strategies.

Subject Keywords

Drug resistance, Cellular DNA barcoding, Colorectal cancer, Tumor heterogeneity

URI

https://hdl.handle.net/11511/116213

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Graduate School of Natural and Applied Sciences, Thesis