Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces significant challenges. These include adverse side effects, lack of tissue specificity, complex regulatory requirements, and the high cost of development and implementation. Addressing these challenges requires a multifaceted approach. Streamlined regulatory pathways and increased funding for translational research can further accelerate the clinical adoption of these agents. This paper reviews the landscape of radioprotector research, examining the biological mechanisms, clinical trials, and challenges that have limited the clinical translation of many promising agents. This review underscores the critical need for continued research and innovation to bridge the gap between experimental radioprotectors and viable clinical treatments, aiming to enhance the therapeutic ratio of radiotherapy in oncology.