Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control

Cancer affects millions of individuals annually, with radiotherapy playing a crucial role in the treatment of over 70% of cases. Nevertheless, the effectiveness of radiotherapy is frequently limited by tumor radioresistance and the associated toxicity to normal tissues. Radiosensitizers enhance tumor sensitivity to ionizing radiation, optimizing doses and reducing damage. This review evaluates diverse radiosensitizers, including natural compounds (curcumin, resveratrol), chemotherapeutics (cisplatin, doxorubicin), and high-Z nanoparticles (gold, hafnium), which amplify DNA damage and ROS production. Advanced nanocarriers-carbon-, lipid-, and polymer-based-improve targeted delivery, specificity, and bioavailability. Various molecular mechanisms involving proteins such as p53, PARP1, miRNAs (miR-21, miR-155), and siRNAs are discussed in relation to their roles in modulating cell cycle progression, apoptosis, and gene expression to overcome resistance. Radioprotectors like antioxidants and amifostine safeguard normal tissues. Ongoing trials with hafnium oxide and cisplatin regimens show promise. Key findings highlight nanotechnology's role in enhancing radiosensitization via dose enhancement factors and synergistic therapies. Implications include personalized treatments tailored to tumor biology, the reduction of radioresistance through precision medicine and data-driven strategies, and ultimately, the improvement of radiotherapy efficacy and patient outcomes.