Abstract
The MDR1 gene encodes P-glycoprotein, a key adenosine triphosphate-dependent efflux pump involved in drug metabolism. Mutations in MDR1 can lead to altered drug transport, contributing to multi-drug resistance in canine lymphoma, which complicates treatment and affects patient survival. The objective of this study was to investigate the relationship between MDR1 mutations and ex vivo drug sensitivities in canine lymphoma patients. Using patient-derived cells from 76 dogs, we assessed cell size, granularity, antigen expression, and drug sensitivity to 12 anti-cancer agents, while also examining clinical outcomes. Our results showed that MDR1-mutated cells exhibited significantly higher ex vivo sensitivity to mitoxantrone, melphalan, and dexamethasone. Additionally, T-cell lymphomas displayed lower drug sensitivity and worse clinical outcomes compared to B-cell lymphomas. Importantly, MDR1-mutated patients demonstrated inferior survival, with a median overall survival of 74 days compared to 204 days for wild-type patients. In this manner, MDR1 mutation is a critical factor influencing drug sensitivity and clinical outcomes in canine lymphomas. Incorporating MDR1 genotyping and ex vivo drug sensitivity testing could enable more personalized and effective treatment strategies, improving both safety and efficacy for affected dogs.
