Veterinary and comparative oncology最新文献

{"title":"Comparison of Volumetric Modulated Arc Therapy and Fixed-Field Intensity-Modulated Radiotherapy for Canine Prostatic Carcinoma Using a 4.3 Gy × 10-Fraction Protocol: A Dosimetric Planning Study.","authors":"MyoungHun Kim, InSeong Jeong, KiDong Eom, JaeHwan Kim","doi":"10.1111/vco.70073","DOIUrl":"https://doi.org/10.1111/vco.70073","url":null,"abstract":"<p><p>Advancements in radiotherapy, including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), have reduced radiation-induced toxicities, enabling hypofractionated protocols to be feasible for treating intrapelvic tumours in dogs. This study aimed to determine the optimal planning technique for canine prostatic carcinoma using a radiotherapy protocol delivering 43 Gy in 10 fractions. Four techniques were compared-two full arcs (2FA), two partial arcs (2PA), 9-field IMRT (9F) and 7-field IMRT (7F). Computed tomography datasets from 22 dogs were analysed. While the conformity index did not differ significantly among techniques, IMRT demonstrated significantly lower homogeneity index than VMAT. IMRT yielded the lowest rectal normal tissue complication probabilities (NTCPs), maximum dose (Dmax) and V45, whereas 2PA achieved the lowest mean dose (Dmean) and V10, V15, V20, V25 and V30. Additionally, IMRT showed significantly lower NTCPs and V20, V25 and V30 for the colon; NTCPs and V20, V25, V30 and V35 for the small intestine; and Dmax, V20, V25 and V45 for the bladder. For the urethra, IMRT showed the lowest Dmax and V45, whereas 2PA demonstrated the lowest Dmean and V10, V15 and V20. The spinal cord (Dmean, V10, V15) and cauda equina (Dmean, Dmax, V10, V15 and V20) were best spared with 2PA. However, 2PA resulted in the highest femoral head NTCPs, Dmean, Dmax and V20, V25 and V30. IMRT showed significantly greater monitor units and beam-on time than VMAT, especially with 9F. In conclusion, under the predefined and unaltered planning objective and constraints used in this study, IMRT showed more favourable OAR sparing and improved dose homogeneity than VMAT. Among the IMRT techniques, 7F may be preferred over 9F due to reduced beam-on time and monitor units. However, these findings reflect the specific equipment, planning setting and optimisation approach applied in this study and different planner, systems or optimisation strategies may yield different results. Therefore, treatment planning should be individualised according to patient-specific dosimetric characteristics.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of the Tumour Microenvironment in Surgically Resected Canine Pulmonary Adenocarcinomas.","authors":"Masanao Ichimata, Yumiko Kagawa, Atsushi Toshima, Fukiko Matsuyama, Eri Fukazawa, Kei Harada, Ryuzo Katayama, Yuko Nakano, Tetsuya Kobayashi, Masaya Igase, Takuya Mizuno","doi":"10.1111/vco.70075","DOIUrl":"https://doi.org/10.1111/vco.70075","url":null,"abstract":"<p><p>The prognostic relevance of the tumour microenvironment in surgically resected canine pulmonary adenocarcinomas (cPACs) remains uncertain. This retrospective single-centre cohort study evaluated associations between intratumoural immune features and postoperative outcomes. Dogs treated between 2005 and 2021 with histologically confirmed cPACs that had undergone surgical excision and had an evaluable tumour microenvironment were included. Immunohistochemistry for CD8, Foxp3, CD3 and CD20 was performed. CD8+ and Foxp3+ cell densities were quantified in five intratumoural hotspots of 0.237 mm² each. Lymphoid aggregates (LAs) were defined as intratumoural aggregates located within tumour nests or intratumoural stroma and composed of at least 50 CD20+ B cells with intercellular spacing ≤ 10 μm and admixed CD3+ T cells. Primary outcomes were progression-free interval (PFI) and overall survival time (OST). A total of 71 dogs were enrolled. LAs were identified in 49 dogs (69.0%). The median densities of CD8+, CD20+ and Foxp3+ cells were 130.0, 398.3 and 79.3 cells/mm², respectively. Tumours with LAs showed higher CD20+ and Foxp3+ cell densities than tumours without LAs. Median PFI and OST were 754 days (95% CI, 375-not reached) and 716 days (95% CI, 399-936), respectively. In multivariable analysis, tumour size classification, lymph node metastasis, surgical margin status and the presence of LAs were independently associated with shorter PFI. Age, lymph node metastasis and the CD8/Foxp3 ratio were independently associated with OST. These findings indicate that immunohistochemical features may provide additional prognostic information for postoperative risk stratification in cPACs and complement established clinicopathological factors.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Response of Canine and Human Osteosarcoma Tumour Cell Lines to Molecularly Targeted Anticancer Agents at Clinically Relevant Exposures With Analysis of Genomic Biomarkers.","authors":"Daniel L Gustafson, Kala A Early, Maritza A Morales, Klaudia A Poplawski, Sunetra Das, Dawn L Duval","doi":"10.1111/vco.70074","DOIUrl":"https://doi.org/10.1111/vco.70074","url":null,"abstract":"<p><p>Osteosarcoma (OSA) is a primary bone tumour occurring in children but is also prevalent in large breed dogs. Canine OSA (cOSA) has long been viewed as analogous to human OSA (hOSA) with cOSA serving as a surrogate for development of therapeutic approaches to treat the rarer human form. Drug therapy of OSA has remained virtually unchanged over the last four decades and drug testing is challenging due to the genomic heterogeneity of OSA as well as the limited number of patients for clinical trials. Thus, an approach that includes a suitable clinical surrogate at the early stage of therapeutic development may be beneficial. Therefore, to address these challenges, a phenotypic drug screen of 12 targeted anticancer drugs was carried out using 13 cOSA and 6 hOSA cell lines and responses compared at clinically relevant exposures (CRE) estimated from human data. The results identified four drugs (alisertib, crizotinib, onvansertib and sorafenib) with significant responses at the CRE in cOSA and hOSA cell lines and demonstrated that drug responses were indistinguishable across species. Correlations of drug response with genomic biomarkers in the cOSA cell line panel identified Myc and Hedgehog signalling as potential predictors of crizotinib response and Myc, epithelial markers and anti-apoptotic signalling for onvansertib response. The conclusions of these findings are that cOSA and hOSA cell lines show the same range of response to targeted agents and identify potential biomarker pathways for further investigation in OSA tumours for use in future comparative oncology studies including clinical trials in pet dogs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine-Enhanced Vaccine as Surgery Adjuvant Treatment for Spontaneous Canine Melanoma: Comparison of Two Intralesional Procedures for Local Disease Control.","authors":"Liliana M E Finocchiaro, Marcela S Villaverde, Gerardo C Glikin","doi":"10.1111/vco.70072","DOIUrl":"https://doi.org/10.1111/vco.70072","url":null,"abstract":"<p><p>We present here the feasibility, safety, and efficacy results of a 7-year study that included 337 canine melanoma patients undergoing surgery with adjuvant intralesional therapies combined with immunogenic therapy. After complete (CS) or partial (PS) surgery, the patients received post-surgical bed injections of (i) lipoplexes carrying canine interferon-β (cIFNβ) gene combined with bleomycin (CT_IF/B) or (ii) 5-fluorouracil (CT_5FU). This surgery adjuvant therapy (SAT) also included the periodic administration of subcutaneous genetic vaccines composed of tumour extracts and lipoplexes carrying cIFNβ, human interleukin-2, and human granulocyte-macrophage colony-stimulating factor genes. Compared at the end of their individual follow-ups with controls treated with complete surgery alone (CSo), CS-CT_IF/B and CS-CT_5FU treatments quadrupled the fraction of local disease-free (from 19% to 81% and 85%), and increased the percentage of metastasis-free patients (M0: from 47% to 82% and 81%). Both PS arms (PS-CT_IF/B and PS-CT_5FU) also significantly increased the fraction of metastatic-free disease (M0: from 48% to 75% and 73%). In addition, SAT produced a significant 11- (CS-CT_IF/B: p < 0.0001, HR_{95% CI} = 0.155 [0.109-0.222]), 9- (CS-CT_5FU: p < 0.0001, HR_{95% CI} = 0.172 [0.123-0.242]), 6- (PS-CT_IF/B: p < 0.0001, HR_{95% CI} = 0.204 [0.132-0.315]), and 7- (PS-CT_5FU: p < 0.0001, HR_{95% CI} = 0.203 [0.132-0.311]) fold increase of overall survival as compared to their respective CSo and PSo controls. The respective median follow-up days for each group were: 695.5 (28-2516), 542.5 (46-2554), 458 (29-1273), and 521 (30-1659). In general terms, this SAT transformed a lethal disease into a manageable condition where 25% (CS-CT_IF/B), 24% (CS-CT_5FU), 22% (PS-CT_IF/B), and 22% (PS-CT_5FU) of patients were still alive at the end of the study, while 53%, 60%, 16%, and 17%, respectively, died from causes unrelated to melanoma. Both surgery adjuvant treatments delayed or prevented post-surgical recurrence and metastases, improved disease-free and overall survival while maintaining quality of life. These successful outcomes encourage assaying a similar scheme for human melanoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Exposures, DNA Methylation and Whole Blood DNA Damage in Pet Golden Retrievers.","authors":"Ashleigh N Tindle, Mark E Berres, Lauren Baker, Zhuonan Wu, Brenna Swafford, Julia Labadie, Lauren A Trepanier","doi":"10.1111/vco.70066","DOIUrl":"https://doi.org/10.1111/vco.70066","url":null,"abstract":"<p><p>Canine multicentric lymphoma (CL) is a common and typically fatal cancer among dogs. Although certain breeds have a higher incidence of CL, its environmental risk factors remain uncertain. Exposures to herbicides and volatile organic compounds (VOCs) associate with non-Hodgkin lymphoma in people. These exposures also correlate with measurable in vivo DNA strand breaks in dogs, even at estimated systemic concentrations that do not reach genotoxic thresholds. Herbicides and VOCs can also exert genotoxicity through differential DNA methylation. We therefore hypothesised that higher chemical exposures would be associated with differential global and gene-specific methylation in the blood of pet golden retrievers, and that differential gene-specific methylation would be further associated with measured DNA strand breaks and oxidised DNA damage. We performed Oxford Nanopore sequencing in 24 of 60 dogs from a recent case-control study within the Golden Retriever Lifetime Study cohort, selected based on the highest and lowest quintiles of estimated aggregate herbicide and VOC exposures. Contrary to our initial hypothesis, higher estimated chemical exposures were associated with relatively lower promoter methylation of antioxidant genes (median 0.335 versus 0.374; p = 0.007) and 8-oxoguanine DNA repair genes (median 0.254 versus 0.294; p = 0.007). This pattern could represent a compensatory response to chemical exposures rather than a driver of DNA damage. Follow-up studies are needed to determine whether these modest promoter methylation differences correspond to biologically meaningful increases in gene expression, antioxidant status and DNA repair capacity.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Analysis of Survival and Adverse Effects Associated With Stereotactic Body Radiation Therapy in 12 Dogs With Hepatocellular Carcinoma.","authors":"Victoria Lee Newberry, Mary-Keara Boss, Del Leary, Tiffany W Martin","doi":"10.1111/vco.70071","DOIUrl":"https://doi.org/10.1111/vco.70071","url":null,"abstract":"<p><p>This retrospective analysis evaluated 12 dogs with hepatocellular carcinoma (HCC) who received stereotactic body radiation therapy (SBRT). Dogs received between 6 and 25 Grey (Gy) per fraction for 1-5 fractions for a total dose of 13-30 Gy. Eleven patients (92%) experienced acute adverse effects (AE), with the majority being VRTOG grade 2-3 stomach/small intestinal AE. Additionally, 70% of patients experienced late AE, with the majority being VRTOG grade 2 stomach/small intestinal AE. Liver-specific side effects were also observed following SBRT, including VCOG-CTCAE grade 4 hepatic encephalopathy and grade 5 liver failure. There was a statistically significant correlation between the gross tumour volume (GTV) and the overall survival time (OST; p = 0.02) as well as a significant correlation between the percentage of normal liver affected by the mass and the severity of acute stomach/small intestinal AE (p = 0.01). Statistically significant correlations were observed between the dose of radiation to the normal liver, starting with a threshold dose of 7 Gy, and an increase of the liver enzyme ALT. Median survival time (MST) of the cohort was 301 days. Dogs with > 28.7% of the liver affected by the mass had a MST of 182 days vs. 419 days for dogs with < 28.7% affected (p = 0.009). This study suggests parameters for GTV, percentage of liver affected, and dose to normal liver could affect survival and the likelihood for adverse effects and liver enzyme elevation when treating with SBRT.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Questions in Genomic Diagnostics for Veterinary Oncology: What We Need to Know.","authors":"Sharadha Sakthikumar, Giulia Siravegna, Michelle E White, Douglas H Thamm, Esther Chon","doi":"10.1111/vco.70068","DOIUrl":"https://doi.org/10.1111/vco.70068","url":null,"abstract":"<p><p>Genomic diagnostics are increasingly integrated into veterinary oncology practice, offering the possibility of refined approaches to tumour classification, risk stratification and therapeutic guidance through high-throughput sequencing technologies. In human medicine, the clinical utility of genomic testing is underpinned by rigorous analytical and clinical validation, robust regulatory oversight and an expanding evidence base linking specific genomic alterations to disease phenotypes and therapeutic responses. In contrast, genomic testing in veterinary oncology remains underdeveloped, with limited standardisation, sparse species-specific validation and frequent reliance on extrapolation from human data. This review delineates the current landscape of genomic testing in veterinary oncology, emphasising methodological considerations in assay design, validation requirements, and clinical interpretation. We highlight the need for analytical rigour, including the use of in silico and orthogonal validation strategies, and advocate for the establishment of performance benchmarks that account for assay sensitivity, specificity and reproducibility in relevant canine populations. In addition, we address the interpretive challenges posed by variants of uncertain significance and the limitations of inferring clinical actionability from human oncology frameworks. A critical, question-driven approach is proposed to guide clinicians in evaluating the validity and applicability of genomic tests, focusing on test validation, intended clinical use and the functional relevance of identified alterations. Advancing genomic diagnostics in veterinary oncology will require coordinated efforts to improve transparency, expand validation cohorts and align clinical expectations with the current evidentiary base. These steps are essential to realising the full potential of precision medicine in veterinary oncology while maintaining scientific and clinical integrity.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.","authors":"Ingrid Marie Moberg, Nina Hansen, Helga Bergholtz, Kaja Sverdrup Borge, Gjermund Gunnes, Ellen Frøysadal Arnet, Ole Albert Guttersrud, Monica Hongrø Solbakken, Frode Lingaas","doi":"10.1111/vco.70067","DOIUrl":"https://doi.org/10.1111/vco.70067","url":null,"abstract":"<p><p>This study presents a comprehensive transcriptomic analysis of 128 canine mammary tumours (CMTs), aiming to characterize their molecular landscape. Differential gene expression analysis (DGE), gene set enrichment analysis (GSEA) and clustering based on the human PAM50 gene panel were applied to explore molecular differences between the different histological categories. The analysis revealed transcriptomic differences between benign and malignant tumours as well as between tumours with high and low mitotic count. Malignant tumours were significantly enriched for gene sets associated with cell cycle regulation, proliferation, inflammatory response, signalling pathways and metabolic processes. Of the malignant tumours, purely epithelial tumours were enriched in gene sets related to proliferation, signalling and metabolic processes when compared to mixed tumours harbouring myoepithelial or mesenchymal components. To assess the relevance of human classification systems, CMTs were clustered on the PAM50 genes. The analysis revealed two clusters resembling human basal-like and luminal A subtypes, while the remaining tumours did not display expression patterns similar to human breast cancer subtypes. This suggests that there are limitations to applying the human molecular classification systems to canine tumours without adaptation. Additionally, CMTs displayed intragroup heterogeneity, where not all tumours within a histopathological category clustered together, indicating that the molecular aspect of CMTs is not necessarily reflected in the pathology. Together, this study highlights the need to develop canine-specific molecular markers based on gene expression, which could enable diagnosis prior to surgical removal of tumours, and ultimately improve treatment strategies and outcomes for dogs with mammary tumours.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Margins Required for the Complete Excision of Canine Oral Melanomas.","authors":"Jonathon Richard Chinner, Jovene Jia Wen Lee, Jonathan Tuke, Fui Wen Yap","doi":"10.1111/vco.70069","DOIUrl":"https://doi.org/10.1111/vco.70069","url":null,"abstract":"<p><p>Oral malignant melanoma (OMM) is the most common canine oral neoplasm. Complete excision is recognised as the mainstay of treatment in the absence of distant metastasis, but recommended surgical margins are unvalidated. This study investigates the surgical margins required for complete excision of canine OMMs. We hypothesised that surgical margins 10-15 mm wide and a qualitative deep margin (bone, fascia or full-thickness tissue excision) would be adequate for complete local excision of OMMs. Margins required to excise canine oral melanocytomas are also unknown; a secondary objective was to investigate this. Cases were retrospectively collected from two referral centres and a veterinary pathology laboratory. Histologic diagnosis, en bloc excision of gross tumour, surgical margin and histologic margins were required for inclusion. Tumours were categorised based on surgical margin width (Group A < 10 mm, Group B 10-15 mm and Group C > 15 mm). A qualitative deep margin was required for Groups B and C, but not Group A, to include marginal excision cases. Histologic margins were classified by the R tumour classification scheme. Twenty-eight tumours were included, comprising 25 OMMs and three melanocytomas. R0 rates for OMMs were 56% (10/17) in Group A, 100% (7/7) in Group B and 100% (2/2) in Group C. Surgical margins ≥ 10 mm were significantly (p = 0.03) more likely to result in R0 classification. The three melanocytomas were all classified as R0, with < 10 mm surgical margins. Results suggest that surgical margins 10-15 mm wide and a qualitative deep margin may be adequate for complete excision of OMMs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Phosphoproteomic Profiling Reveals Stage-Specific Signalling and Metabolism in Equine Melanocytic Neoplasm.","authors":"Paitoon Srimontri, Amornthep Kingkaw, Nawarus Prapaiwan, Rangsima Sujittosakul, Nichapat Iamkaewprasert, Jiraschaya Piputwat, Puetta Isama-Al, Thanutchanok Munkongdee, Thanapon Chotikaprakal, Petchpailin Yanyongsirikarn, Narumon Phaonakrop, Sittiruk Roytrakul, Wanwipa Vongsangnak, Parichart Tesena","doi":"10.1111/vco.70070","DOIUrl":"https://doi.org/10.1111/vco.70070","url":null,"abstract":"<p><p>Equine melanocytic neoplasms (EMN) are aggressive tumours characterised by high metastatic potential and limited therapeutic options available. However, the molecular mechanisms underlying their progression remain poorly understood. This study therefore presents the integrative phosphoproteomic analysis of EMN tissue, with the aim of elucidating stage-specific alterations in signalling pathways and metabolism. Nineteen tissue samples from grey horses were categorised as normal-stage (n = 6), early-stage EMN (n = 7), and severe-stage EMN (n = 6) and subjected to in-depth analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 2035 phosphoproteins were identified, of which 219 were differentially expressed across the disease stages. Interestingly, early-stage EMN showed dysregulation of inositol phosphate metabolism and activation of the PI3K-Akt pathway which involved INPP5F and PKN2. In severe-stage EMN, upregulation of SYNJ1, STRN4 and VIM indicated enhanced membrane trafficking, cytoskeletal remodelling, and MAPK signalling. Additionally, ASPM and GNAO1 upregulation reflected heightened proliferation and altered Rap1 signalling, while UBR5 dysregulation suggested aberrant protein homeostasis. Metabolic reprogramming was also noticed, with elevated TKT and GAPDH expression supporting glycolysis and NADPH production. Observably, the severe-stage EMN exhibited a higher expression of Dickkopf-3 (DKK3) which suggests a role in aberrant Wnt/β-catenin activation and tumour progression. These findings reveal stage-specific molecular mechanisms in EMN pathogenesis and highlight potential biomarkers and therapeutic targets for equine melanoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}