The Hidden Treasures of Biobanks: Unlocking the Value of Archived Tissue
1. Introduction
For decades, fresh-frozen tissue has served as the gold standard for molecular research. Yet the strict preservation demands and specialized storage requirements of fresh-frozen samples make them expensive and challenging to use in broad retrospective research [1].
In contrast, formalin-fixed, paraffin-embedded (FFPE) samples have quietly preserved the “secrets” of human disease within biobanks. Each sample stored in these archives is linked to a distinct clinical history and outcome. Despite their long-recognized value as data assets, FFPE metabolomics has been challenging and historically limited for deep metabolomic profiling because of the chemical cross-linking introduced by formalin fixation. However, advances in optimized workflows are increasingly making FFPE metabolomics feasible [2,3].
Panome Bio’s TissueBridge™ Metabolomics is one example of such an approach, applying a combination of tailored sample preparation, high-resolution mass spectrometry, and advanced computational analysis to enable metabolomic profiling of archived FFPE tissue to archived FFPE tissue [4]. More broadly, these developments highlight the growing potential of FFPE archives for retrospective metabolomic and translational research.
2. “Back to the Future”
The scale of the FFPE resource is extraordinary. Prospective studies can take years to collect sufficient fresh-frozen samples and await results, while biobanks already store FFPE samples linked to decades of clinical follow-up data, ready for use [5]. This makes true retrospective profiling possible, allowing researchers to look back at treatment response, disease progression, and long-term outcomes, and to relate these trajectories to the metabolic state present at the time of tissue collection [6].
By not limiting themselves to prospective collections of fresh-frozen tissue, researchers can significantly shorten the path to biomarker discovery. This is particularly important for rare diseases and narrowly defined cancer subtypes, where assembling new cohorts is often slow, costly, and scientifically challenging, making retrospective analysis of archived samples especially valuable [7]. In this context, archival tissue samples become more than just preserved FFPE specimens; they are a resource for investigating scientific questions that were not even considered at the time of collection.
3. From Degradation Concerns to Analytical Feasibility
Long-standing technical concerns have suggested that formalin fixation alters tissue chemistry through cross-linking, metabolite loss, and fixation-related reaction products, thereby complicating deep metabolomic analysis of FFPE tissue [3,7]. However, emerging FFPE-optimized workflows indicate that biologically meaningful metabolite information can still be recovered from archived tissue. By combining tailored sample preparation, complementary chromatographic strategies, and high-resolution mass spectrometry, these approaches make it increasingly feasible to analyze FFPE specimens in a metabolomics context. Importantly, comparisons between matched FFPE and fresh-frozen samples have shown that key biological patterns can remain conserved across preservation methods. Taken together, these observations support the view that archived FFPE tissue may serve as a valuable resource for retrospective metabolomic research and translational studies [4,8].
4. Metabolic Signatures of Tumor Biology
Retrospective metabolomic analysis of colorectal cancer tissue can reveal core features of tumor bioenergetics, including the shift toward aerobic glycolysis classically described as the Warburg effect. In this setting, alterations in tricarboxylic acid cycle intermediates, including elevated succinate and reduced fumarate, may be consistent with reduced succinate dehydrogenase activity and broader metabolic rewiring associated with tumor progression [9]. Succinate is also recognized as an oncometabolite capable of inhibiting α-ketoglutarate-dependent dioxygenases, thereby influencing DNA and histone methylation, while changes in methionine-cycle intermediates may reflect altered one-carbon metabolism involved in methylation reactions and redox balance [10,11,12]. Within this broader analytical context, workflows such as TissueBridge™ are of interest because they may allow these pathway-level metabolic features to be examined in archived FFPE tissue, extending metabolomic investigation into retrospective and clinically annotated specimen collections [4].
5. Massive Insight from a Microscopic Slice
A practical advantage of FFPE-oriented metabolomics workflows is their small tissue requirement, which may make them well suited to scarce archival specimens and more compatible with multi-omic study design. Because FFPE tissue is routinely stored at room temperature and represents the most common archival material in pathology departments and biobanks, such approaches have clear relevance for retrospective research [13]. Panome Bio’s TissueBridge™ workflow is designed to operate withing this framework. is one example of this type of workflow. In its published materials, the company states that the method can be applied to approximately 10 mg of tissue obtained from 2–3 sections of a standard FFPE block and is intended to generate reproducible untargeted metabolomic data from archived samples [4]. This limited sample footprint may also help preserve material for complementary analyses, an important consideration as integrated multi-omics approaches become more common in translational research [14]. These characteristics may be particularly valuable for rare diseases and uncommon tumor subtypes, where prospective fresh-frozen collection is often slow and logistically difficult [15].
6. Retrospective Multi-Omics and the Functional Readout of Archived Tissue
As translational research moves toward multi-omic integration, metabolomics is often treated as a particularly informative layer because it reflects downstream biochemical activity shaped by both genetic and environmental influences. At the same time, archived FFPE tissue is increasingly being used for retrospective biomarker work, including analyses based on stored clinical-trial specimens [16].
Within that context, FFPE-compatible workflows may help extend multi-omic investigation to clinically annotated archival material. Rather than suggesting that archived tissue can simply “rescue” failed drug programs, a more precise interpretation is that retrospective reanalysis of preserved specimens may help identify responder subgroups, refine biomarker hypotheses, and support more targeted follow-up development strategies. This use of archived specimens for prognostic and predictive biomarker evaluation is already well established methodologically, and multi-omic analyses of FFPE samples have already been used to study treatment-response biology, including response to anti-PD-1 therapy in melanoma [16,17].
In this broader analytical landscape, TissueBridge™ can be mentioned as one example of an FFPE-oriented metabolomics workflow intended to expand the utility of archived pathology material, while the larger point remains platform-agnostic: retrospective multi-omic profiling of FFPE tissue may help connect archived specimens to response biology in a way that is relevant for translational research and precision medicine [4].
7. Conclusion
Biobanks have always been built on the idea of preserving value for the future. Today, FFPE archives are proving just how powerful that idea can be.
What was once seen mainly as stored pathology material is increasingly becoming a source of new translational insight. With the rise of FFPE-compatible metabolomics and other multi-omic workflows, archived tissue can now do more than document the past, it can help answer some of the most important questions in disease research today.
Emerging analytical technologies are unlocking deeper, more comprehensive metabolome coverage, enabling researchers to extract meaningful biological insight from even highly challenging sample types.
The hidden treasure of biobanks is no longer hidden. It is sitting in archived collections around the world, waiting for the right technologies to unlock it. Contact us for more information.
Refrences
- Alsawaf, Y., Maksimovic, I., Zheng, J., Zhang, S., Vuckovic, I., Dzeja, P., Macura, S., & Irazabal, M. V. (2024). A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results. American journal of physiology. Renal physiology, 327(5), F697–F711. https://doi.org/10.1152/ajprenal.00131.2024
- Dapic, I., Uwugiaren, N., Kers, J., Mohammed, Y., Goodlett, D. R., & Corthals, G. (2022). Evaluation of Fast and Sensitive Proteome Profiling of FF and FFPE Kidney Patient Tissues. Molecules (Basel, Switzerland), 27(3), 1137. https://doi.org/10.3390/molecules27031137
- Wojakowska, A., Marczak, Ł., Jelonek, K., Polanski, K., Widlak, P., & Pietrowska, M. (2015). An optimized method of metabolite extraction from formalin-fixed paraffin-embedded tissue for GC/MS analysis. PloS One, 10(9), e0136902. https://doi.org/10.1371/journal.pone.0136902
- TissueBridge™ | Next-Generation Metabolomics for FFPE Samples. Panomebio.com. Retrieved March 13, 2026, from https://panomebio.com/resources/tissuebridge-next-generation-metabolomics-for-ffpe-samples/
- Serdar, C. C., Cihan, M., Yücel, D., & Serdar, M. A. (2021). Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochemia medica, 31(1), 010502. https://doi.org/10.11613/BM.2021.010502
- Piehowski, P. D., Petyuk, V. A., Sontag, R. L., Gritsenko, M. A., Weitz, K. K., Fillmore, T. L., Moon, J., Makhlouf, H., Chuaqui, R. F., Boja, E. S., Rodriguez, H., Lee, J. S. H., Smith, R. D., Carrick, D. M., Liu, T., & Rodland, K. D. (2018). Residual tissue repositories as a resource for population-based cancer proteomic studies. Clinical Proteomics, 15(1), 26. https://doi.org/10.1186/s12014-018-9202-4
- Dannhorn, A., Swales, J. G., Hamm, G., Strittmatter, N., Kudo, H., Maglennon, G., Goodwin, R. J. A., & Takats, Z. (2022). Evaluation of Formalin-Fixed and FFPE Tissues for Spatially Resolved Metabolomics and Drug Distribution Studies. Pharmaceuticals (Basel, Switzerland), 15(11), 1307. https://doi.org/10.3390/ph15111307
- Cacciatore, S., Zadra, G., Bango, C., Penney, K. L., Tyekucheva, S., Yanes, O., & Loda, M. (2017). Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues. Molecular cancer research : MCR, 15(4), 439–447. https://doi.org/10.1158/1541-7786.MCR-16-0262
- Cai, R., Ke, L., Zhao, Y., Zhao, J., Zhang, H., Zheng, P., Xin, L., Ma, C., & Lin, Y. (2025). NMR-based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages. International journal of cancer, 156(8), 1644–1655. https://doi.org/10.1002/ijc.35273
- Eijkelenkamp, K., Osinga, T. E., Links, T. P., & van der Horst-Schrivers, A. N. A. (2020). Clinical implications of the oncometabolite succinate in SDHx-mutation carriers. Clinical genetics, 97(1), 39–53. https://doi.org/10.1111/cge.13553
- Ducker, G. S., & Rabinowitz, J. D. (2017). One-Carbon Metabolism in Health and Disease. Cell metabolism, 25(1), 27–42. https://doi.org/10.1016/j.cmet.2016.08.009
- Liao, M., Yao, D., Wu, L., Luo, C., Wang, Z., Zhang, J., & Liu, B. (2024). Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer. Acta pharmaceutica Sinica. B, 14(3), 953–1008. https://doi.org/10.1016/j.apsb.2023.12.003
- Kokkat, T. J., Patel, M. S., McGarvey, D., LiVolsi, V. A., & Baloch, Z. W. (2013). Archived formalin-fixed paraffin-embedded (FFPE) blocks: A valuable underexploited resource for extraction of DNA, RNA, and protein. Biopreservation and biobanking, 11(2), 101–106. https://doi.org/10.1089/bio.2012.0052
- Gegner, H. M., Naake, T., Aljakouch, K., Dugourd, A., Kliewer, G., Müller, T., Schilling, D., Schneider, M. A., Kunze-Rohrbach, N., Grünewald, T. G. P., Hell, R., Saez-Rodriguez, J., Huber, W., Poschet, G., & Krijgsveld, J. (2024). A single-sample workflow for joint metabolomic and proteomic analysis of clinical specimens. Clinical proteomics, 21(1), 49. https://doi.org/10.1186/s12014-024-09501-9
- Garcia, M., Downs, J., Russell, A., & Wang, W. (2018). Impact of biobanks on research outcomes in rare diseases: a systematic review. Orphanet journal of rare diseases, 13(1), 202. https://doi.org/10.1186/s13023-018-0942-z
- Simon, R. M., Paik, S., & Hayes, D. F. (2009). Use of archived specimens in evaluation of prognostic and predictive biomarkers. Journal of the National Cancer Institute, 101(21), 1446–1452. https://doi.org/10.1093/jnci/djp335
- Garg, S. K., Welsh, E. A., Fang, B., Hernandez, Y. I., Rose, T., Gray, J., Koomen, J. M., Berglund, A., Mulé, J. J., & Markowitz, J. (2020). Multi-Omics and Informatics Analysis of FFPE Tissues Derived from Melanoma Patients with Long/Short Responses to Anti-PD1 Therapy Reveals Pathways of Response. Cancers, 12(12), 3515. https://doi.org/10.3390/cancers12123515
