Dissecting Epigenetic Drug Response Mechanisms Using CRISPR Knockout Screens

Epigenetic drugs are widely applied in cancer therapy due to their ability to modify gene expression without altering the DNA sequence. Despite their therapeutic potential, drug resistance frequently occurs, posing a significant challenge in cancer treatment. CRISPR screens have emerged as a powerful tool to address this issue by leveraging the precision of CRISPR-Cas9 gene editing to enable the systematic interrogation of genes. This approach involves the simultaneous targeting of thousands of genes to elucidate their roles in various biological processes, disease mechanisms, and drug responses, providing valuable insights into gene function and potential therapeutic targets. In cancer therapy, CRISPR screens provide a deeper understanding of cancer progression by enabling the identification of essential genes and facilitating the discovery of novel therapeutic targets when combined with epigenetic drugs. Here, we present an overview of the CRISPR screen methodology, which involves introducing guide RNAs targeting specific genes into cells, followed by phenotype selection and analysis.