Longitudinal assessment of B-RAF V595E levels in the peripheral cell-free tumor DNA of a 10-year-old spayed female Korean Jindo dog with unresectable metastatic urethral transitional cell carcinoma for monitoring the treatment response to a RAF inhibitor (sorafenib)

• Published in: The Veterinary quarterly Vol. 41; no. 1; pp. 153 - 162
• Main Authors: Kim, Jung-Hyun, Ahn, Dana Hyunjung, Moon, Je-Sung, Han, Hyun-Jung, Bae, Kieun, Yoon, Kyong-Ah
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Ltd 01.12.2021; Taylor & Francis; Taylor & Francis Group
• Subjects: Anticancer properties; Antineoplastic drugs; Antitumor activity; Antitumor agents; b-raf v595e; Case Report; circulating cell-free tumor dna; Deoxyribonucleic acid; DNA; dog; Dogs; Enzyme inhibitors; ErbB-2 protein; Kinases; Metastases; Metastasis; Monitoring; Mutation; Patients; Protein-tyrosine kinase receptors; Raf gene; Raf protein; sorafenib; Tissues; Transitional cell carcinoma; Tumors; Tyrosine; Urinary tract; vascular endothelial growth factor; Vascular endothelial growth factor receptors; sorafenib; circulating cell-free tumor DNA; B-RAF V595E; Dog; transitional cell carcinoma; vascular endothelial growth factor
• ISSN: 0165-2176; 1875-5941
• DOI: 10.1080/01652176.2021.1905194

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 , and , 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 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.