Kieun Bae

Hepatic neuroendocrine carcinoma (NEC) in dogs is a rare malignancy with limited therapeutic guidance and no established standard of care. This report describes an adaptive, clinically guided multimodal treatment approach in a dog with advanced hepatic NEC with regional lymph node involvement. Sequential systemic therapies—including doxorubicin, mitoxantrone with lomustine and prednisolone, and subsequently toceranib—were administered based on clinical response assessment using imaging (VCOG RECIST), hematologic monitoring, and quality-of-life evaluation. Ex vivo drug sensitivity testing (DST) was performed to provide functional reference information but was interpreted as supportive rather than predictive. Notably, discordance was observed between strong in vitro sensitivity to doxorubicin and early clinical progression, underscoring the limitations of monoculture-based assays in recapitulating in vivo tumor biology. Sustained stable disease was observed following transition to toceranib with continued adjunct immunomodulatory therapy; however, the independent contribution of each treatment component cannot be determined. This case highlights the feasibility of iterative treatment refinement in rare canine malignancies and emphasizes that DST findings should be integrated cautiously within a broader clinical decision-making framework.

Small bowel obstruction (SBO) in dogs is most commonly caused by foreign bodies or neoplasia; however, SBO secondary to transmural fibroplasia remains a rare clinical complication of canine chronic enteropathy. This report describes the complex case of mechanical SBO caused by transmural ileal fibroplasia and inflammation at the ileocolic junction in a 9-year-old mixed-breed dog with concomitant hyperadrenocorticism (HAC). The primary presentation involved chronic severe weight loss and intermittent anorexia, contrasting with the acute presentation typical of most SBO cases. Imaging studies revealed severe, circumferential thickening up to 10 mm of the small intestine wall at the ileocolic junction (ICJ), resulting in complete luminal stricture and marked proximal dilation. Surgical intestinal resection and anastomosis were performed for alleviation of the obstruction, and histopathology confirmed severe mural and serosal enteritis with extensive fibroplasia extending into the adjacent mesentery, thereby excluding neoplastic processes. Quantitative PCR analysis demonstrated a significant upregulation of mRNA expression for PDGFRB and FGFR compared to normal tissue. Postoperative recovery was rapid; although soft feces persisted for one month, normal stool consistency was subsequently restored, and the patient achieved significant weight gain. This case underscores the diagnostic and therapeutic challenges associated with non-neoplastic, inflammation-driven SBO and suggests that activation of the PDGFR-β/FGFR pathways may play a key role in fibroplasia-related intestinal strictures, offering a novel molecular perspective beyond conventional SBO etiologies.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract. In this case study, a dog with metastatic urethral TCC was treated with sorafenib. The tumor expression levels of receptor tyrosine kinase genes, including VEGFR-1, VEGFR-2, PDGFR-α, PDGFR-β, ALK, EGFR, ErbB2, and B-RAF, were analyzed. VEGFR was overexpressed in tumor tissues compared to the normal tissues. Considering the high frequency of B-RAF mutation in canine urological tumors, the B-RAF gene was examined, and the B-RAF V595E mutation was detected in the tumor tissue. Therefore, the antitumor effect of sorafenib, a multi-tyrosine kinase inhibitor, on unresectable metastatic urethral TCC characterized by B-RAF V595E was evaluated and circulating cell-free tumor DNA (ctDNA) was assessed for monitoring the treatment response. After the initiation of oral sorafenib therapy (4 mg/kg/day escalated to 10 mg/kg/day), the dysuria was alleviated gradually, and the patient remained stable for 3 months. During that treatment period, the patient showed various levels of changes associated with B-RAF V595E mutation in ctDNA as evident from longitudinal plasma samples after initiation of sorafenib therapy. The findings of this study suggest that ctDNA may serve as a useful non-invasive tool for monitoring the treatment response to anticancer drugs.