Abolfazl Bemidinezhad
1,2,3, Yasaman Abolhassani
4, Mojgan Noroozi-Karimabad
1, Arman Abroumand Gholami
5, Abbas Alalikhan
3,6,7, Ramin Roshani
8, Mohammad Parsa-kondelaji
9, Fatemeh Gheybi
4,10* 
1 Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
2 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4 Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Department of Chemistry, Faculty of Education, Al-Ayen Iraqi University, Thi-Qar, Iraq
7 Department of Laboratory Medicine, Nasiriyah Heart Hospital, Thi-Qar Health Directorate, Nasiriyah, Iraq
8 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
9 Basic Science Department, Neyshabur University of Medical Science, Neyshabur, Iran
10 Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Cancer treatment has advanced significantly, yet traditional modalities such as radiotherapy still encounter challenges, including damage to healthy tissues and limited tumor specificity. Monoclonal antibodies (mAbs) have emerged as powerful tools in oncology, offering particular therapeutic options with reduced toxicity. Their capacity to enhance the efficacy of radiotherapy through radiosensitization presents a promising strategy for improving cancer outcomes. This review synthesizes findings from the past decade, providing an in-depth analysis of the diverse roles of mAbs in radiosensitization. Key mechanisms are discussed, including targeting molecular pathways, modulation of immune responses, and integration with novel platforms such as nanoparticles and antibody-drug conjugates (ADCs). The review also highlights the successes of preclinical and clinical studies while addressing ongoing challenges like delivery inefficiencies, tumor resistance, and antigen heterogeneity. Additionally, emerging alternatives including aptamers, nanobodies, and engineered proteins are explored as potential solutions to these barriers. Advancements in mAb-based delivery systems and combination therapies remain crucial for achieving more personalized and effective cancer treatments.