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Purpose of Review Precision oncology increasingly depends on accurate molecular and functional characterization of tumor tissue across genomic, transcriptomic, proteomic, epigenetic, and live-cell applications. This review evaluates how commonly used tissue preservation methods, including formalin-fixed paraffin-embedded (FFPE), fresh, flash-frozen, and cryopreserved tissue, affect downstream analytical fidelity and translational utility. Recent Findings Recent comparative studies demonstrate that FFPE remains effective for histopathology and a few established molecular assays but introduces nucleic acid fragmentation, crosslinking, deamination artifacts, protein modification, and loss of cellular viability. These effects can reduce sequencing efficiency, alter quantitative molecular measurements, and limit applications requiring intact proteins or viable cells. In contrast, flash-frozen and cryopreserved tissues generally provide greater molecular fidelity, while controlled-rate cryopreservation additionally preserves viable cellular populations for single-cell analysis, organoid development, functional precision medicine, tumor-infiltrating lymphocyte expansion, and CAR-T manufacturing. Emerging evidence also supports the use of cryopreserved living tumor biobanks for longitudinal and functional testing. Summary No single preservation method is optimal for every application. FFPE remains essential for routine pathology, whereas flash freezing is well suited for high-fidelity molecular profiling and controlled-rate cryopreservation offers the broadest compatibility with both molecular and live-cell applications. Prospective biospecimen strategies that align tissue preservation with anticipated diagnostic, molecular, functional, and therapeutic uses may improve the reliability and clinical utility of precision oncology.
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Beltran et al. (2026) studied this question.
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