**3. β-Lapachone, a DNA repair inhibitor**

*Translational Research in Cancer*

**2. Radiotherapy as a single agent**

**2.1 Initial use of ionizing radiation**

agents used in the clinic in comparison with NAD(P)H quinone oxidoreductase-1 (NQO1)-bioactivatable drugs. β-Lapachone (β-Lap) is a clinical chemotherapeutic agent discovered to be a potent DNA repair inhibitor in the late 1980s. It has since been shown to be bioactivated by NQO1, an enzyme elevated more than 20-fold in most solid human cancers, e.g., non-small cell lung, pancreas, prostate, head and

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,

neck, and breast cancers, and shows promise as a potent radiosensitizer.

including combination with chemotherapeutics or radiosensitizers.

**Radiosensitizer Tumor type Mechanism** Hyperbaric oxygen Brain tumors Oxygenation Nicotinamide Glioblastoma Oxygenation Metronidazole Cervical cancer Oxygenation Mitomycin-C Breast cancer Kills hypoxic cells 5-fluorouracil (5FU) Gastrointestinal S-phase check points Bromodeoxyuridine (BrDU) Breast Repair inhibition Topo-inhibitors Breast, cervical DNA damage **NBTXR3** Solid tumors Direct

**Nimoral** Head and neck Modifies hypoxia **Trans sodium crocetinate** Glioblastoma Oxygenation **NVX108** Glioblastoma Oxygenation

*The last four are emboldened to denote their current use in ongoing clinical trials.*

*List of commonly used radiosensitizing methods/agents for combination with radiotherapy in various tumor types.* 

Radiosensitizing agents are molecules that enhance the dose of ionizing radiation delivered to a patient's tumor. The optimal clinical radiosensitizer (a) lowers the required dose of ionizing radiation, (b) increases its antitumor effect, and

**2.2 Enhancing radiation therapy with radiosensitizers**

**144**

**Table 1.**

*Clinical radiosensitizers.*
