Atomic force microscopy in lung cancer: from mechanobiology to clinical translation

Atomic force microscopy (AFM) enables the nanoscale investigation of cellular mechanics, morphology, and molecular interactions under conditions that closely mimic physiological environments. This review synthesizes AFM analytical methodologies relevant to lung cancer, evaluating their applications in cell mechanics, early diagnosis, drug screening, and personalized therapy. Notable analytical advancements include the validation of cell stiffness as a mechanobiological biomarker, the development of AFM-based liquid biopsies with improved efficiency for capturing circulating tumor cells, and the incorporation of artificial intelligence for automated classification. A critical analysis of technical limitations addresses issues such as standardization, throughput, and controversies in data interpretation, as well as regulatory challenges that hinder clinical translation. Emerging trends include in vivo AFM, the integration of multi-omics approaches, and mechanoadjuvant strategies.