Proteomics in Veterinary Oncology: A Deeper Look at What Tumors Are Actually Doing
Cutting Edge Diagnostics · Canine, Feline · Oncology
Genomics has dominated the conversation around precision oncology for the past decade — and for good reason. The ability to sequence a tumor's DNA and identify driver mutations has reshaped cancer biology across species. DNA tells you the potential. Proteomics tells you the reality. The distinction matters, and it is one reason proteomics is attracting increasing attention as a complementary layer of tumor characterization in both human and veterinary oncology.
What proteomics is
Proteomics is the large-scale study of the proteome — the complete set of proteins expressed by a cell, tissue, or organism at a given point in time. Where genomics characterizes the static blueprint of a cell's DNA, proteomics captures the dynamic output: which proteins are being produced, at what quantities, in what modified forms, and how they interact.
This distinction is not semantic. A gene may be present and intact but silenced, underexpressed, or post-translationally modified in ways that alter its function. Conversely, a tumor may express proteins at levels that bear no straightforward relationship to gene copy number. DNA gives you the potential; proteomics gives you the reality. The proteome reflects the actual functional state of a cell — its metabolic activity, signaling pathway activation, stress responses, and interactions with the surrounding microenvironment — in ways that genomic data alone cannot.
Modern proteomic analysis is largely mass spectrometry-based. Proteins are extracted from tissue or biofluid, digested into peptides, separated chromatographically, and analyzed by mass spectrometry to identify and quantify thousands of proteins simultaneously. Advances in sample preparation, instrument sensitivity, and computational analysis have made proteomics applicable to increasingly small tissue samples, including formalin-fixed paraffin-embedded (FFPE) material — the standard archive format in histopathology — which opens the door to retrospective studies on existing tissue banks.
Why proteomics matters for cancer biology
Cancer is fundamentally a disease of dysregulated protein function. Oncogenes drive tumor growth through constitutively active proteins; tumor suppressor genes lose function when their protein products are absent, truncated, or modified. The signaling cascades that drive proliferation, evasion of apoptosis, angiogenesis, and metastasis are all mediated by proteins — and by the post-translational modifications (phosphorylation, glycosylation, ubiquitination) that regulate protein activity, localization, and degradation.
IHC, the most familiar protein-based tool in diagnostic pathology, addresses a narrow slice of this landscape — the expression of individual proteins selected in advance based on known diagnostic or prognostic relevance. Proteomics takes an unbiased, discovery-oriented approach: rather than asking whether a specific protein is present, it asks what the full protein landscape of the tumor looks like and how it differs from normal tissue or from other tumor types. This untargeted approach has the potential to identify biomarkers, pathway activations, and tumor classifications that targeted assays would never find because no one thought to look for them.
Current applications in canine oncology
Canine oncology has been the primary driver of veterinary proteomics research, partly because of the clinical infrastructure supporting canine cancer studies and partly because canine tumors serve as validated models for human cancers with shared biological features.
Mast cell tumor proteomics has received meaningful attention given MCT's status as the most common canine skin tumor and the clinical significance of grade and mutation status for treatment decisions. Proteomic profiling of canine MCTs has identified differentially expressed proteins between high-grade and low-grade tumors, some of which are not captured by current histologic grading criteria or c-Kit mutation status. These findings suggest that the proteome carries prognostic information that grade and IHC do not fully account for — though the translation from research finding to validated clinical tool has not yet occurred.
Canine osteosarcoma (OSA) is another area of active proteomic investigation, driven by the high metastatic rate, poor long-term prognosis, and limited treatment advances in this tumor type. Proteomic studies of OSA have characterized the tumor secretome — the proteins actively secreted by tumor cells — and identified candidate serum biomarkers that may reflect tumor burden or metastatic activity. The ability to detect OSA-associated proteins in peripheral blood before metastasis becomes radiographically apparent would represent a meaningful advance in monitoring, but validation in prospective clinical cohorts remains the necessary next step.
Canine lymphoma proteomics has explored differences between B-cell and T-cell subtypes at the protein level and investigated drug resistance mechanisms in relapsed cases. Some proteomic studies have identified metabolic reprogramming — shifts in energy metabolism pathways — as a distinguishing feature between treatment-responsive and treatment-refractory lymphomas, pointing toward potential therapeutic vulnerabilities.
Mammary gland tumors in dogs have also been profiled proteomically, with studies identifying proteins associated with invasive versus non-invasive phenotypes and with metastatic potential. Given that canine mammary tumors are used as models for human breast cancer research, these findings have dual relevance — to veterinary clinical care and to the broader cancer biology literature.
Current applications in feline oncology
Feline proteomics research lags canine by a meaningful margin, reflecting the broader pattern of smaller research investment in feline cancer biology. However, several tumor types have received proteomic attention, and the feline literature is growing.
Feline oral squamous cell carcinoma — discussed previously in this blog as one of the most consistently fatal oral malignancies in cats — has been the subject of proteomic profiling aimed at understanding the molecular basis of its aggressive behavior and resistance to treatment. Proteomic studies have identified pathway activations consistent with the EGFR and COX-2 dysregulation known from IHC and molecular studies, and have identified additional candidate targets in cell adhesion and invasion pathways. These findings are consistent with the histopathologic picture of FOSCC as a deeply invasive, desmoplastic tumor and offer potential future therapeutic angles, though clinical translation is not yet established.
Feline injection-site sarcoma has also been examined proteomically, with findings that complement the IHC and molecular data on PDGFR dysregulation and immune microenvironment composition. The intersection between proteomic profiling and the tumor-associated macrophage research in FISS represents an area where the two approaches inform each other — proteomic characterization of macrophage phenotypes within the tumor can provide a more complete picture of the immune microenvironment than IHC alone.
Feline lymphoma, particularly the small cell versus large cell distinction in alimentary disease that carries significant prognostic and management implications, has been approached proteomically in a small number of studies. Differentiating these subtypes by proteomics rather than relying solely on morphology and IHC is a logical goal given how consequential the distinction is clinically, and preliminary data suggest proteomic profiles differ between these entities in ways that may ultimately support diagnostic refinement.
The relationship between proteomics and histopathology
Proteomics does not replace histopathology — and the relationship between the two is worth framing carefully. Histopathology provides tissue architecture, cellular morphology, spatial context, and the morphologic characterization of lesions that proteomic data cannot replicate. A mass spectrometry result does not tell you whether cells are arranged in trabeculae or sheets, whether the tumor is infiltrating bone or abutting a fascial plane, or whether the surgical margin is clear. These are questions that require a pathologist and a microscope.
What proteomics adds is a molecular layer that contextualizes and extends the morphologic diagnosis. A histologically intermediate-grade mast cell tumor with a proteomic profile consistent with aggressive behavior is a different clinical entity than the same morphologic grade with a proteome resembling low-grade tumors. A feline oral SCC with activated invasion pathway proteins identified proteomically may warrant a different prognosis communication than one without those activations — even if the H&E appearance is similar.
The most productive vision for proteomics in veterinary oncology is integrative: histopathology as the diagnostic foundation, proteomics as a refinement layer that adds precision to prognosis, treatment selection, and monitoring. The parallel to IHC is instructive — IHC did not replace H&E, it extended it. Proteomics may ultimately occupy a similar relationship to both.
Where this is going
Several developments are likely to shape the trajectory of veterinary proteomics over the next five years. FFPE proteomics is the most immediately practical, because it makes existing tissue archives accessible for proteomic analysis without requiring fresh frozen tissue prospectively. As protocols for FFPE protein extraction and mass spectrometry analysis continue to improve, retrospective studies on well-characterized tumor cohorts with known outcomes will accelerate biomarker discovery and validation.
Plasma and serum proteomics — identifying tumor-derived or tumor-associated proteins in peripheral blood — represents the liquid biopsy analog in the proteomic space. Where ctDNA liquid biopsy detects tumor-derived nucleic acids, plasma proteomics detects secreted or shed proteins. The two approaches are complementary and may ultimately be used together to build a more comprehensive picture of tumor biology from a blood draw. Commercial development of plasma proteomic panels for veterinary cancer detection and monitoring is a plausible near-term development, though validated assays do not yet exist.
Spatial proteomics — mapping protein expression across tissue sections while preserving spatial context — is an emerging methodology that directly bridges the gap between proteomics and histopathology. Rather than homogenizing tissue and losing architectural information, spatial proteomics allows protein quantification at the cellular or subcellular level within intact tissue sections, preserving the relationship between proteomic data and tissue morphology. This approach is in early development in human pathology and will likely reach veterinary research applications within the decade.
The practical question for the next several years is not whether proteomics will contribute to veterinary oncology — it already is — but how quickly research findings will translate into validated, clinically deployable tools. That translation requires prospective cohort studies with sufficient sample sizes, standardized protocols, and outcome data. The veterinary oncology community is building that infrastructure, and the pace is accelerating.
Eric Snook, DVM, PhD, DACVP — Vetopathy. Histopathology remains the diagnostic foundation. Emerging molecular tools like proteomics are most powerful when they extend and refine what tissue morphology already tells us.