Radiation therapy (RT) is commonly used to treat solid tumors, using high-energy radiation like X-rays to kill cancer cells. While effective, it has side effects and can lead to resistance in some tumors. A new approach aims to improve RT by targeting a protein called BRD4, which becomes more active in response to RT and helps tumor cells resist treatment. This project combines expertise from four research groups in Belgium and China to develop a novel therapy. The therapy uses special proteins called PROTACs, which can degrade BRD4. These PROTACs are attached to another protein, MATRAC, that targets tumors by responding to the acidic environment found in many cancers. This combination aims to specifically target and eliminate senescent tumor cells (old or damaged cells that have stopped dividing but can promote cancer growth) and enhance the effectiveness of RT. The research involves several steps: (1) Designing and Producing the Therapy: Creating the PROTAC-MATRAC proteins and testing their ability to bind to cancer cells in acidic conditions. (2) Testing in Cells: Evaluating how well the therapy works in cell cultures, including its ability to degrade BRD4 and kill cancer cells. (3) Animal Testing: Studying the therapy's effects in mice with tumors, including how well it distributes in the body and targets tumors. (4) Monitoring Treatment: Developing new tools to monitor how effectively the therapy induces tumor cell senescence in real-time.