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Overcoming Innate And Acquired Therapy Resistance By Targeting Dna Repair In Human Cancer Cells, Mateusz Rytelewski

Electronic Thesis and Dissertation Repository

Genomic instability and a high mutation rate lead to heterogeneity in human tumors. Mathematical modelling predicts that these characteristics promote acquired resistance to cytotoxic and targeted therapies, by increasing the likelihood that resistant subpopulations exist at the start of treatment (and promoting the accumulation of de novo resistance mutations during treatment). As a result, genome plasticity promotes increased fitness on the population level, but individual tumor cells must nonetheless maintain a level of DNA integrity that allows for continued survival, particularly in the context of DNA-damaging therapy (which DNA repair counteracts). Thus, DNA repair proteins are a source of innate …