The Young's Modulus as a Mechanical Biomarker in AFM Experiments: A Tool for Cancer Diagnosis and Treatment Monitoring.

This review explores recent advances in data processing for atomic force microscopy (AFM) nanoindentation on soft samples, with a focus on "apparent" or "average" Young's modulus distributions used for cancer diagnosis and treatment monitoring. Young's modulus serves as a potential key biomarker, distinguishing normal from cancerous cells or tissue by assessing stiffness variations at the nanoscale. However, user-independent, reproducible classification remains challenging due to assumptions in traditional mechanics models, particularly Hertzian theory. To enhance accuracy, depth-dependent mechanical properties and polynomial corrections have been introduced to address sample heterogeneity and finite thickness. Additionally, AFM measurements are affected by tip imperfections and the viscoelastic nature of biological samples, requiring careful data processing and consideration of loading conditions. Furthermore, a quantitative approach using distributions of mechanical properties is suitable for tissue classification and for evaluating treatment-induced changes in nanomechanical properties. As part of this review, the use of AFM-based mechanical properties as a tool for monitoring treatment outcomes-including treatments with antifibrotic drugs and photodynamic therapy-is also presented. By analyzing nanomechanical property distributions before and after treatment, AFM provides insights for optimizing therapeutic strategies, reinforcing its role in personalized cancer care and expanding its applications in research and clinical settings.