White Paper | December 11, 2025
Mass Spectrometry-Based FFPE Proteomics as a Transformational Platform for Modern Oncology R&D
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White Paper Download - FFPE Proteomics vs. IHC
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The field of oncology has entered an era in which therapeutic efficacy is determined not by simple binary biomarkers, but by complex and dynamic protein networks that control tumor growth, immune evasion, and drug response or resistance. Despite this complexity, the diagnostic backbone of modern oncology continues to rely heavily on immunohistochemistry (IHC), a technique that while historically transformative was developed more than eighty years ago and is fundamentally constrained by its architecture.
IHC offers a limited, semi-quantitative window into tumor biology, typically measuring a single to handful of proteins at a time, using antibodies whose specificity, reproducibility, and performance often vary across laboratories and even between lots. As therapeutics become more mechanistically nuanced, and as precision oncology shifts toward understanding pathway activation, immune cell states, and proteomic signatures, the constraints of IHC have become a bottleneck for biomarker development, clinical trial efficiency, and therapeutic innovation.
In contrast, recent advances in mass spectrometry (MS)–based proteomics have enabled high-resolution, quantitative analysis of formalin-fixed, paraffin-embedded (FFPE) tumor samples, the tissue type used universally in clinical practice. These technological developments in MS-based FFPE proteomics now allow comprehensive measurement of more than 10,000 proteins from a single 5 μm FFPE curl or slide, with levels of precision, reproducibility, and analytic depth that were not attainable even several years ago.
Explore how the emergence of clinically robust MS-based FFPE proteomics represents a pivotal moment for oncology: for the first time, it is possible to directly quantify the functional protein landscape of a tumor, including protein isoforms, post-translational modifications (PTMs), signaling pathway activation, immune cell states, and resistance mechanisms, all without reliance on antibodies.
This white paper describes the scientific limitations of IHC, outlines the capabilities of MS-based FFPE proteomics, and illustrates how proteomics provides unique strategic advantages in drug discovery, translational biology, biomarker development, clinical trial execution, and clinical deployment.
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Strategic Applications for MS-Based Proteomics Across the Drug Development Lifecycle
The capabilities of MS-based FFPE proteomics align closely with the needs of modern oncology drug development.
The discovery phase increasingly relies on understanding how signaling networks interact and how tumor and immune cell states evolve under therapeutic influence. Because it is nontargeted, MS-based FFPE proteomics reveals unexpected proteins and processes that would not be measured with predefined, constrained IHC panels. It provides the depth necessary to detect pathway activation, signaling dependencies, protein isoforms, and post-translational regulation that genomics cannot predict. This reduces false positives in target nomination and grounds early drug development evaluations in functional biology rather than inferred hypotheses.
In translational research, MS-based FFPE proteomics allows researchers to develop multi-analyte signatures that integrate information from dozens of pathways, providing clarity on mechanism-of-action, target engagement, pathway modulation, and emergent resistance biology. Such signatures can capture T-cell activation states, exhaustion biology, antigen presentation competence, macrophage polarization patterns, metabolic reprogramming, or stress-response modules. These insights inform translational oncology teams about which assets have true mechanistic differentiation and which are likely to face challenges during clinical advancement. None of these multi-layered biological processes can be reliably measured using IHC due to its limited multiplexing capacity and dependence on antibodies.
MS-based FFPE proteomics can also be used in clinical development to improve patient stratification by identifying biomarker profiles of likely responders and non-responders, and elucidating the emergent resistance mechanisms that often drive late-stage trial failures. The ability to directly analyze proteins in FFPE tissue at scale ensures compatibility with clinical archives and multicenter trials, enabling retrospective studies that would otherwise be impossible. These insights allow clinical oncology teams to de-risk clinical programs, optimize indication selection, and justify expanded line-of-therapy positioning based on mechanistic differentiation.
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White Paper Download - FFPE Proteomics vs. IHC
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