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)

Veterinary Quarterly

Kyong-Ah Yoon¹  Kieun Bae¹  Jung-Hyun Kim²  Dana Hyunjung Ahn³  Hyun-Jung Han⁴  Je-Sung Moon⁴ 

[1] Department of Veterinary Biochemistry, College of Veterinary Medicine, Konkuk University;Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University;Department of Veterinary Internal Medicine, Konkuk University Veterinary Medical Teaching Hospital;Veterinary Emergency Medicine and Critical Care, Konkuk University Veterinary Medical Teaching Hospital;

关键词: dog;    transitional cell carcinoma;    circulating cell-free tumor dna;    b-raf v595e;    vascular endothelial growth factor;    sorafenib;   

DOI  :  10.1080/01652176.2021.1905194

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown