Biomarkers of radioresistance in lung cancer: Current insights and future directions (Review)

Radiotherapy (RT) remains a cornerstone of lung cancer (LC) management, serving as either a definitive treatment or an adjuvant modality following surgical resection. Nevertheless, a major challenge for radiation oncologists is the emergence of radioresistance, whether intrinsic or acquired, which contributes to therapeutic failure, tumor recurrence, metastasis and ultimately to increased patient mortality. Radioresistance is a multifactorial process driven by genetic and epigenetic alterations that dysregulate key signal transduction pathways, enabling cancer cells to survive and adapt under radiotherapeutic stress. A deeper understanding of the molecular mechanisms underlying radioresistance is therefore essential to identify robust biomarkers for patient stratification, prognostication and therapeutic targeting. Such insights could enable individualized treatment strategies within the framework of precision oncology and inform the development of novel radiosensitization approaches to overcome resistance in LC. The present review synthesized current evidence on molecular biomarkers associated with RT resistance in LC.