IDENTIFYING EPIGENETIC MODIFICATIONS TO COMBAT RESISTANCE TO THE CHEMOTHERAPEUTIC AGENT DOXORUBICIN

There has been substantial progress in cancer research that has markedly enhanced patient outcomes. However, chemotherapy resistance persists and often leads to multidrug resistance, rendering cancer cells unresponsive to multiple chemotherapy drugs, presenting a significant challenge in the effective treatment of the disease. Dysregulation in gene expression patterns caused by abnormalities in epigenetic mechanisms have been identified as contributing factors to the development and progression of cancer. Epigenetic research offers potential to discover drugs that target specific epigenetic modifications to regulate gene expression patterns in the context of chemotherapy resistance. I hypothesize that histone modifications on histone H3 and histone H4 contribute to doxorubicin resistance. The data presented here provides an initial screening of the mutant monoallelic histone yeast strains to identify post-translationally modifiable amino acids in H3 and H4 that could contribute to doxorubicin resistance. The possible targets of histone modifications were then repeated in triplicate to obtain statistical significance. Finally, Western blot techniques were used to identify the modification occurring on the histone H3 and histone H4 amino acid sites that were previously identified to be statistically significant.