Myriad factors and pathways influencing tumor radiotherapy resistance

Radiotherapy is a cornerstone in the treatment of various tumors, yet radioresistance often leads to treatment failure and tumor recurrence. Several factors contribute to this resistance, including hypoxia, DNA repair mechanisms, and cancer stem cells. This review explores the diverse elements that drive tumor radiotherapy resistance. Historically, resistance has been attributed to cellular repair and tumor repopulation, but recent research has expanded this understanding. The tumor microenvironment - characterized by hypoxia, immune evasion, and stromal interactions - further complicates treatment. Additionally, molecular mechanisms such as aberrant signaling pathways, epigenetic modifications, and non-B-DNA structures play significant roles in mediating resistance. This review synthesizes current knowledge, highlighting the interplay of these factors and their clinical implications. Understanding these mechanisms is crucial for developing strategies to overcome resistance and improve therapeutic outcomes in cancer patients.