**2.1 Initial use of ionizing radiation**

The late 19th-century discovery of the X-ray by Wilhelm Roentgen led to diagnostic tools and therapies for diseases such as blood disorders and benign and malignant growths [1, 2]. Initially, radiation was delivered using unfocused beams, causing skin and blood malignancies in both patients and radiologists [1, 2]. Today, patients benefit from vast technological improvements, allowing for focused radiation beams, which markedly increased patient survival. Current approaches include conformal radiation therapy, proton beam radiation therapy, stereotactic radiation therapy (using linear accelerators or gamma knife devices), and intraoperative therapy [3]. Despite improvements in targeting tumors and reducing normal tissue damage, high doses of radiation are still required for a curative effect. Some tumors can also be resistant to radiotherapy, including hypoxic tumors and dormant cancer cells that regrow when the optimal tumor microenvironment presents itself. Thus, methods to improve the safety and efficacy of ionizing radiation were initiated, including combination with chemotherapeutics or radiosensitizers.
