DNA damage repair (DDR) pathways are essential for maintaining genomic integrity and cellular homeostasis. In cancer, these pathways are often dysregulated, leading to genomic instability that promotes tumor progression. At the same time, many tumors remain partially reliant on specific DDR mechanisms for survival, making them vulnerable to synthetic lethality approaches. This has led to the development of DDR inhibitors (DDRis), such as PARP, ATR, ATM, and CHK1 inhibitors, which have shown clinical efficacy in several malignancies, including breast, ovarian, and prostate cancers. DDR inhibitors not only impair tumor cell survival but also modulate the tumor microenvironment, influence immune responses, and interact with other stress-response pathways. Despite encouraging clinical results, the molecular consequences of DDRi treatment—especially their impact on global gene regulation—remain incompletely understood. Identifying transcriptional signatures associated with DDR inhibition is essential for understanding resistance mechanisms, optimizing drug combinations, and discovering biomarkers of response. This project aims to characterize the gene expression changes induced by different classes of DDR inhibitors in tumor models. We will use both established cancer cell lines and mouse tumor models to assess transcriptomic alterations following treatment with selected DDRis. RNA sequencing will be performed to capture genome-wide expression changes, and bioinformatic analyses will identify affected pathways, regulatory networks, and candidate genes involved in therapy response or resistance.