Abstract
The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one of the most intensively studied mechanisms of drug resistance in many tumors. In canine lymphoma, it has also been shown that the overexpression of drug efflux pumps such as P-glycoprotein is associated with drug-resistant phenotypes. Canine lymphoma has many pathological similarities to human non-Hodgkin’s lymphoma, and they also share similar molecular mechanisms of drug resistance. We have previously demonstrated the association of the overexpression of drug transporters with drug resistance and indicated some molecular mechanisms of the regulation of these transporters’ expressions in canine and human lymphoid tumor cells. However, it has also been indicated that other known or novel drug resistance factors should be explored to overcome drug resistance in lymphoma. In this review, we summarize the recent findings on the molecular mechanisms of drug resistance and possible strategies to develop better treatment modalities for canine lymphoma from the comparative aspects with human lymphoid tumors.
Highlights
Lymphoma is the most common hematologic neoplasm in dogs [1], and it is a representative neoplasm that responds to conventional chemotherapy such as CHOP, which comprises cyclophosphamide, doxorubicin, vincristine and prednisolone
We previously examined the mRNA expression of the Lung Resistance Protein (LRP) gene in dogs with lymphoma, but there was no significant difference between dogs with and without drug resistance [19]
We examined the DNA methylation status in the promoter regions of the ABCB1 gene in 27 canine B-cell lymphoma patients [63], but the CpG island of this gene was hypomethylated in most dogs in both the chemotherapy-sensitive and -resistant patient groups, which meant that the DNA methylation status might not change during treatment in dogs with B-cell lymphoma
Summary
Lymphoma is the most common hematologic neoplasm in dogs [1], and it is a representative neoplasm that responds to conventional chemotherapy such as CHOP, which comprises cyclophosphamide, doxorubicin, vincristine and prednisolone. Most canine patients with lymphoma undergo relapses, and efficacy of rescue protocols is limited owing to the development of resistance to the agents used in remission-induction therapy. Based on these backgrounds, the molecular mechanisms of the drug resistance in lymphoma cells have been intensively investigated for the development of more effective treatments for canine lymphoma, and most studies have focused on the overexpression of drug transporters such as P-glycoprotein (P-gp). We summarize the recent findings on the molecular mechanisms of drug resistance and possible strategies to develop better treatment modalities for canine lymphoma from the comparative aspects with human medicine
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
