Biophysical approaches to cancer diagnostics: Collagen biomarkers in colorectal cancer

Collagen remodeling in the extracellular matrix drives alterations in the physical, mechanical, and optical properties of tissues, representing a fundamental biophysical hallmark of colorectal cancer (CRC) progression. These changes, reflected in variations in collagen composition, molecular orientation, and cross-linking density, transform tissue stiffness, elasticity, and anisotropy, directly influencing cancer cell behavior and mechanotransduction. Understanding these structural and physical transitions requires analytical methods capable of probing the molecular origins of biomechanical alteration in situ. Spectroscopic and optical methodologies provide high-resolution, label-free detection of the vibrational, optical, and mechanical alteration associated with collagen remodeling. These techniques capture the shifts in molecular vibrational modes, nonlinear optical responses, and scattering anisotropy that arise from collagen fibril alignment, structural disorder, and cross-link formation, thereby connecting molecular architecture to measurable macroscale biomechanics. The integration of multimodal spectroscopy and incorporation of machine learning algorithms further enhance diagnostic performance by resolving complex tissue heterogeneity and improving tumor margin detection. Overall, this review demonstrates how spectroscopic techniques can be applied in the biomedical field for cancer detection by analyzing collagen remodeling and structural alterations.