From diagnostic marker-to-therapeutic modality: emerging paradigms in tumor biomineralization.

Biomineralization is a highly regulated, multi-scale biological process that is well-characterized in physiologic contexts but remains poorly understood in pathologic settings. Tumor-associated calcification frequently occurs in clinical practice but is often regarded as an imaging feature rather than an active biological phenomenon. Existing evidence has indicated that tumor calcification is closely linked to cancer progression, prognosis, and underlying biological behavior. This review synthesizes current knowledge on tumor-associated biomineralization from a multidisciplinary perspective, integrating insights from oncology, cell biology, pathology, materials science, and systems biology. The major types and microstructural features of calcium deposition that occur in tumors are summarized and the clinical correlations are discussed. The proposed molecular and cellular mechanisms, including organelle-mediated mineral nucleation, metabolic regulation, differentiation-driven processes, and cell fate-dependent pathways, were further examined. Advances in multi-omics technologies, biomimetic models, and analytical characterization methods are highlighted as critical enablers for mechanistic investigation across biological scales. Finally, emerging strategies that exploit induced tumor calcification using engineered materials as a potential drug free therapeutic and diagnostic approach are discussed. By framing tumor calcification as an active, regulated phenotype, this review aims to provide a unified conceptual framework, identify current knowledge gaps, and encourage future research toward translational applications in cancer diagnosis and treatment.