Search Results (116)

The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well. Compared with the original cells, the expression of gene encoding for receptors and enzymes belonging to the endocannabinoid system has been found to be altered in several tumor types; it has been hypothesized that this aberrant expression may be related to the course of the neoplasm as well as to the patient’s prognosis. Several studies, conducted both in vitro and in vivo, suggest that both endo- and phytocannabinoids can modulate signaling pathways, controlling cell proliferation and survival. In the complex process of carcinogenesis, cannabinoids seem to intervene at different levels by stimulating cell death, inhibiting the processes of angiogenesis and metastasis, and regulating antitumor immunity. Although the molecular mechanisms by which cannabinoids act are not always clear and defined, their synergistic activity with the most used antineoplastic drugs in clinical oncology is showing promising results, thus providing veterinary medicine with alternative therapeutic targets in disease control. This review aims to summarize current knowledge on the potential role of the endocannabinoid system and exogenous cannabinoids in oncology, with specific reference to the molecular mechanisms by which cannabinoids may exert antitumor activity. Additionally, it explores the potential synergy between cannabinoids and conventional anticancer drugs and considers their application in veterinary oncology. Full article

Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article

Osteosarcoma (OSA) is the most common primary bone malignancy in dogs, characterized by aggressive growth and high metastatic potential. Despite advances in treatment, the prognosis for affected animals remains poor, mainly due to metastatic disease. Metastasis is a complex process that involves forming new blood vessels in the primary tumor (angiogenesis), intravasation, the transport of cancer cells to other locations, extravasation, and the growth of cancer cells in the secondary site. Gold nanoparticles (AuNPs), due to their unique physicochemical properties, are considered promising tools in cancer therapy, both as drug delivery systems and potential anti-metastatic agents. Previously, it has been demonstrated that 500 µg/mL glutathione-stabilized gold nanoparticles (Au-GSH NPs) inhibit cancer cell extravasation—one of the steps of the metastatic cascade. This study aimed to evaluate the anti-metastatic properties of Au-GSH NPs through their influence on OSA cell migration, proliferation, and colony formation in vitro, as well as their antiangiogenic properties on the chick embryo chorioallantoic (CAM) model. Additionally, we investigated whether these effects are associated with changes in alpha-2-macroglobulin (A2M) expression, as it was previously demonstrated to play an essential role in the metastatic cascade. Au-GSH NPs significantly inhibited migration and colony formation in canine osteosarcoma cells (from OSCA-8, OSCA-32, and D-17 cell lines) at 200 µg/mL concentrations. Interestingly, at 500 µg/mL, Au-GSH NPs inhibited angiogenesis on the CAM model and cancer cell migration, but fewer colonies were formed. These results may be directly related to the higher efficiency of Au-GSH NPs uptake by OSA cells at the dose of 200 μg/mL than at the dose of 500 μg/mL, as demonstrated using Microwave Plasma Atomic Emission Spectroscopy (MP-AES). Moreover, this is the first study that demonstrates a significant increase in A2M expression in cancer cells after Au-GSH NPs treatment. This study provides new insight into the potential use of Au-GSH NPs as anti-metastatic agents in canine osteosarcoma, indicating that their anti-metastatic properties may be related to A2M. However, further in vitro and in vivo studies are needed to explore the molecular mechanism underlying these effects and to evaluate the clinical relevance of AuNPs in veterinary oncology. Full article

Background: Canine oral melanoma (COM) is an aggressive and often fatal neoplasm in dogs, with clinical and molecular similarities to human melanoma. Despite its relevance as a comparative oncology model, the molecular mechanisms underlying COM remain poorly understood. This study aimed to characterize gene expression profiles in COM to identify differentially expressed genes (DEGs), potential biomarkers, and therapeutic targets. Methods: In this pilot study, we performed RNA sequencing (RNA-seq) on tumor and healthy oral tissue samples from dogs. Two independent analytical pipelines—Bowtie2-DESeq2 and HISAT-StringTie-Ballgown—were used to ensure robustness in DEG detection. We also conducted pathway enrichment and isoform-level analyses to investigate biological processes and alternative splicing events. Results: Both approaches identified a core set of 929 common DEGs. Key oncogenic pathways, including MAPK/ERK and cell cycle regulation, were significantly affected, with notable upregulation of BRAF, NRAS, CDK4, and MITF (log2FC = 2.86, p < 0.001). The transcription factor SOX10 and the cytokine IL-33, both previously implicated in melanoma progression, were consistently overexpressed. Additionally, NF1, a known RAS pathway inhibitor, was also upregulated. Isoform analysis revealed novel transcript variants, suggesting a complex layer of post-transcriptional regulation in COM. Many DEGs remained uncharacterized, and chromosomal distribution analysis highlighted potential genomic influences. Conclusions: Our findings provide new insights into the molecular landscape of COM, reinforcing its utility as a model for human melanoma. The identification of conserved oncogenic pathways and novel transcript variants opens avenues for further functional studies and the development of targeted therapies in both veterinary and human oncology. Full article

Introduction: Chemotherapy is a primary treatment option in human and veterinary oncology. Like humans, canine patients often develop drug resistance. Comparative oncology is gaining increasing interest, and spontaneous tumors of companion dogs have emerged as a powerful resource for better understanding human cancer. The genetic, molecular, and histological features of tumors in dogs are more closely related to those in humans than the ones in laboratory animals, including complex mechanisms of drug resistance. Methods: A comprehensive literature search was conducted in the electronic database Clarivate Web of Science (WOS): Medical Literature Analysis and Retrieval System Online (MEDLINE) from 1990 to 2025 (updated 22 January 2025). The final set includes 59 relevant full-text English articles. Results: The literature findings suggest that canine spontaneous tumors are valuable model systems with important translational implications for identifying novel mechanisms of chemotherapy resistance shared with humans and may help advance the current standard of care in precision medicine. Conclusions: We have provided an updated overview of the role of canine tumor models to study oncotherapy resistance, focusing on limitations and opportunities for advancement. Despite complementary benefits of such models in translational oncology research, their relevance remains underestimated. Strengthening the collaboration between human and veterinary medicine professionals and comparative medicine researchers, and obtaining the support of interdisciplinary institutions, could contribute to addressing the problem of multidrug resistance for both human and canine patients. Future research may promote using canine spontaneous tumors as translational therapeutic models for human chemoresistance, through a multidisciplinary approach based on the emerging “One Health, One Medicine” paradigm. Full article

Background/Objectives: Cancer stem cells (CSCs) represent a minor yet critical subpopulation within tumors, endowed with self-renewal and differentiation capacities, and are implicated in tumor initiation, progression, metastasis, therapeutic resistance, and recurrence. Reliable in vitro functional assays to characterize CSCs are pivotal for the development of personalized oncology strategies. This study sought to establish and validate a microfluidic device (MD) platform for the enrichment, functional assessment, and therapeutic evaluation of CSC populations derived from experimental models and primary tumor samples. Methods: Murine (LM38LP) and human (BPR6) breast cancer cell lines were cultured within MDs to promote sphere formation. CSC enrichment was confirmed through the expression analysis of pluripotency-associated genes (Oct4, Sox2, Nanog, and CD44) by quantitative PCR (qPCR) and immunofluorescence. Sphere number, size, and gene expression profiles were quantitatively assessed before (control) and after chemotherapeutic exposure. To validate the MD platform against conventional scale, parallel experiments were performed in 12 well plates. To extend translational relevance, three primary canine tumor samples (solid thyroid carcinoma, simple tubular carcinoma, and reactive lymph node) were mechanically disaggregated and processed within MDs for CSC characterization. Results: The MD platform enabled the consistent enrichment of CSC populations, showing significant modulation of sphere growth parameters and stemness marker expression following chemotherapeutic treatment. Beyond its comparability with conventional culture, the MD also supported immunofluorescence staining and allowed real-time monitoring of individual cell growth. Sphere formation efficiency (SFE) and CSC marker expression were similarly demonstrated in primary veterinary tumor cultures, highlighting the device’s cross-species applicability. Conclusions: Microfluidic-based sphere assays represent a robust, reproducible, and scalable platform for the functional interrogation of CSC dynamics and therapeutic responses. This methodology holds great promise for advancing CSC-targeted therapies and supporting personalized oncology in both human and veterinary settings. Full article

Canine transmissible venereal tumor (CTVT) is a contagious neoplasm with low metastatic potential, primarily affecting free-roaming and stray dogs. Despite its global presence, epidemiological data from some regions remain limited. This study employed a retrospective observational design and analyzed 131 CTVT cases diagnosed via cytology or histopathology at a veterinary teaching hospital in Belo Horizonte, Brazil, aiming to describe the anatomical distribution, treatment outcomes, and epidemiological patterns. Most affected dogs were mixed-breed (70.2%) and female (61.1%), with a median age of 4.5 years. Genital involvement was most common (87.0%), followed by cutaneous (10.7%), nasal (6.1%), and oral (4.6%) tumors. Concurrent tumor locations included genital-cutaneous (5.3%) and oronasal (3.1%). Females had more genital cases, while males were more likely to present cutaneous and nasal CTVT, with 5.2 times greater odds for nasal tumors (OR = 5.2; 95% CI = 1.2–25.9). Purebred dogs also had increased odds of nasal involvement (OR = 8.2; 95% CI = 1.9–40.7). Vincristine chemotherapy was effective, and the number of sessions required for a complete response was not associated with clinical presentation, breed or size. These findings highlight the varied presentations of CTVT and reinforce the need for clinical awareness of non-genital forms. Full article

Osteosarcoma (OSA) is a naturally occurring malignant bone tumor in both humans and canines that is characterized by aggressive local behavior and a high propensity for metastasis. Despite advances in diagnostic methods and therapies, long-term survival rates have remained stagnant, underscoring the great need for the development of biomarkers serving in the prognosis and diagnosis of OSA across species. Biomarkers, molecular indicators of disease presence or progression, are pivotal tools in oncology, offering the potential to determine risk stratification, guide targeted therapies, and monitor treatment response. This review provides an in-depth analysis of the current landscape of OSA biomarkers, highlighting diagnostic and prognostic markers identified across species. We highlighted the role of biomarkers, including protein, cellular, metabolic, imaging, genetic, and epigenetic markers, in osteosarcoma diagnosis and prognosis and categorized them across multiple domains. Furthermore, this review explores the utility of the canine model in osteosarcoma research, emphasizing its relevance to human OSA due to comparable diagnostic approaches, prognostic indicators, and clinical manifestations. With this review, we aim to demonstrate that integrating biomarker research across species can deepen the understanding of osteosarcoma pathogenesis and advance knowledge of its underlying biology, ultimately paving the way for precision medicine strategies that benefit both human and veterinary oncology. Full article

Inter-individual variations in drug responses are major concerns in cancer treatment in human and veterinary oncology. Consequently, preclinical models have been proposed to predict drug responses and determine optimal individualized therapy. We aimed to evaluate the clinical utility of in vitro drug sensitivity testing using a patient-derived cell culture model to select appropriate adjuvant therapies for dogs with solid tumors. We screened medical records of 126 dogs with suspected tumors, including 33 dogs with solid tumors (guided group, 16; empirical group, 17). Anticancer drugs used for adjuvant therapy were determined based on in vitro drug sensitivity testing (guided group) or histopathological examination (empirical group) results. Time to tumor progression (TTP) was compared between groups. The guided group had significantly longer TTP than the empirical group (949 vs. 109 days). Median TTPs were significantly longer in the guided group than in the empirical group for dogs with incomplete surgical margin (949 vs. 109 days), dogs with mitotic count < 20 per 10 high power fields (949 vs. 105 days), dogs with no evidence of metastatic disease at initial diagnosis (455 vs. 196 days), and dogs receiving tyrosine kinase inhibitors (949 vs. 109 days). Our study suggests that in vitro drug sensitivity testing may be a useful tool for optimizing adjuvant therapy in dogs with solid tumors. Full article

This review summarizes the findings of veterinary clinical trials on immunogene therapy published between 2017 and 2024. Various tumor types, including melanoma (canine and feline), mastocytoma (canine), mammary adenocarcinoma (canine), osteosarcoma (canine), and sarcoid (equine), were treated using diverse strategies. Non-viral vectors were predominantly used to deliver genes encoding tumor-associated antigens, cytokines, or suicide enzymes. Among these non-viral methods, electrotransfer was the most commonly employed technique for introducing therapeutic genes into cells. Generally, these procedures resulted in minimal or no adverse side effects, and treated animals often showed significant improvements, such as enhanced quality of life, delayed or suppressed tumor recurrence or metastasis, and increased survival times. Some of these innovative approaches hold great potential as adjunct therapies to standard treatments. The promising outcomes from immunogene therapy studies in companion animals strongly support their application in veterinary oncology and provide valuable preclinical data (including safety assessments and proof-of-concept studies) for analogous human clinical trials. Full article

The existence of considerable interpatient variability in pharmacokinetic exposure necessitates dose adjustment to avoid potential adverse events and suboptimal efficacy in targeted therapy. Exposure–response relationships for toceranib phosphate (TOC), the most commonly used tyrosine kinase inhibitor in veterinary oncology, remain unclear. Correlations between TOC exposure and efficacy and safety were evaluated in dogs with solid tumors in our study. Plasma TOC was analyzed at 6 and 48 h post-administration. For the 10 dogs in the exposure–response analysis, the mean interpatient variabilities in dose-normalized peak (C_max) and trough (C_min) concentrations were 29% and 61%, respectively. Dose-normalized C_max did not differ among weeks 1, 4, and 12 (p = 0.414), suggesting that steady-state plasma levels can be achieved within 1 week. Pharmacokinetic exposure at steady state was not significantly associated with efficacy (week 1 C_max, p = 0.941; average C_max, p = 0.548). C_max was positively but nonsignificantly associated with the risk of adverse events (week 1 C_max, p = 0.190; average C_max, p = 0.109). These findings suggest the value of pharmacokinetic monitoring in optimizing TOC dosage and reducing its adverse effects in dogs with solid tumors. Clinicians should consider plasma TOC when managing TOC treatment in small-animal practice. Full article

Cold atmospheric plasma (CAP) is emerging as an innovative approach for cancer treatment because of its selectivity for malignant cells and absence of significant adverse effects. While modern oncological therapies face challenges such as tumor heterogeneity and treatment resistance, CAP presents itself as a low-cost and environmentally sustainable alternative. Its mechanisms of action involve reactive oxygen and nitrogen species (RONS), UV radiation, and electromagnetic fields, which induce cell death. Preclinical and clinical studies have demonstrated the efficacy of CAP, with devices such as dielectric barrier discharge (DBD) and the plasma jet developed to minimize damage to healthy cells. Some CAP devices are already approved for clinical use, showing safety and efficacy. However, the standardization of treatments remains a challenge due to the variety of devices and parameters used. Although CAP has shown promising cytotoxic effects in vitro and in animal models, especially in different cancer cell lines, further research, particularly in vivo and in veterinary medicine, is needed to optimize its clinical use and maximize its efficacy in combating cancer. Full article

Breast cancer remains a significant global health issue, affecting both humans and companion animals, particularly female dogs and cats, where mammary tumors are among the most common cancers. Strategies to minimize the impact of this disease on patients, pet owners, and veterinary medicine are essential. This study analyses the effects of resistance training on the development of chemically induced mammary cancer in female Wistar rats, divided into four groups: sedentary control (CTR), sedentary induced (CTR+N-methyl-N-nitrosourea (MNU)), exercised control (EX), and exercised induced (EX+MNU). The exercise protocol involved ladder climbing three times a week for 18 weeks with the load progressively increasing. At the study’s end, blood and histopathological samples were collected and analyzed. Although tumor onset occurred two weeks earlier and incidence was slightly higher in the exercised group (EX+MNU) compared to the control group (CTR+MNU), the mortality rate was lower, and the malignancy was not as aggressive. No systemic inflammation was observed, as the levels of albumin, C-reactive protein (CRP), and interleukin 6 (IL-6) in the MNU groups remained similar to the controls. Exercise has been shown to promote overall health by increasing physical fitness, boosting immunological function, and improving metabolic health. These findings may offer valuable insights into the potential role of resistance training in managing mammary cancer in companion animals. However, further research is required to assess clinical applicability and to establish safe and effective exercise protocols for veterinary oncology. Full article

Captive birds of prey often exceed their wild counterparts’ lifespan, as seen in bald eagles (Haliaeetus leucocephalus, ~20 years wild vs. ~40 years captive), golden eagles (Aquila chrysaetos, ~32 years wild vs. ~46 years captive), and Andean condors (Vultur gryphus, ~50 years wild vs. ~79 years captive), highlighting the impact of controlled environments on longevity. However, recent evidence suggests a rising incidence of neoplastic processes in these species. While previous studies have indicated a higher-than-expected prevalence of neoplasia in raptors, comprehensive research on this topic remains scarce. Squamous cell carcinoma (SCC), a frequently reported neoplasm in pet birds, has been documented in birds of prey, though the literature on its prevalence and management is limited. Retrospective studies have identified SCC cases in peregrine falcons (Falco peregrinus), primarily affecting the flank or thigh, with locally invasive behavior and rare distant metastasis. Complete surgical excision is the preferred treatment for SCCs, yet its feasibility is often constrained by tumor invasiveness and anatomical limitations. Electrochemotherapy (ECT) has emerged as a promising alternative, utilizing electroporation to enhance intracellular drug uptake while minimizing systemic toxicity. Bleomycin and cisplatin have been successfully used in avian intralesional chemotherapy, offering a potentially safer and effective treatment approach. ECT has demonstrated efficacy in various exotic species, yet its application in raptors remains largely unexplored. This case report describes the use of electrochemotherapy with bleomycin in a peregrine falcon diagnosed with SCC, contributing to the growing body of evidence supporting its clinical utility in avian oncology. Full article

Feline mammary carcinoma (FMC) is an aggressive neoplasm with a poor prognosis. Clinical staging is crucial for risk assessment, yet the current WHO system lacks granularity, particularly in Stage III. Aligning this system with human breast cancer staging has the potential to improve prognostic accuracy. Additionally, prognostic factors such as tumor size, ulceration, lymph node metastasis, and lymphovascular invasion require further evaluation. This study retrospectively analyzed 75 female cats with FMC to assess the prognostic impact of clinicopathological factors and evaluate a novel staging system (new staging) adapted from the AJCC Cancer Staging Manual. Survival analyses included disease-free interval (DFI), and overall survival (OS). Tumor size >3 cm (p < 0.001), ulceration (p = 0.010), lymphovascular invasion (p < 0.001), lymph node metastasis (p < 0.001), WHO and new staging (p < 0.001) were significantly associated with shorter survival. The new staging refined Stage III into III_A (T₃N₀M₀), III_B (T₄N₀M₀), and III_C (AnyTN₁M₀), improved prognostic differentiation. Stage III_C cases had the worst survival (p < 0.001). Multivariate survival analysis identified lymphovascular invasion (HR = 2.834, 95% CI: 1.546–5.195, p = 0.001), histological Grade II (HR = 5.013, 95% CI: 1.122–22.397, p = 0.035) and III (HR = 9.894, 95% CI: 2.195–44.594, p = 0.003) and skin ulceration (HR = 2.462, 95% CI: 1.256–4.825, p = 0.009). These findings support the prognostic relevance of key clinicopathological factors in FMC and highlight the advantages of a refined TNM-based staging system, which may enhance risk stratification and therapeutic decision-making in veterinary oncology. Full article