Leflunomide Suppresses the Growth of LKB1-Inactivated Tumors in the Immune-Competent Host and Attenuates Distant Cancer Metastasis.

ABSTRACT: Liver kinase B1 (LKB1)-inactivated tumors are vulnerable to the disruption of pyrimidine metabolism, and leflunomide emerges as a therapeutic candidate because its active metabolite, A77-1726, inhibits dihydroorotate dehydrogenase, which is essential for de novo pyrimidine biosynthesis. However, it is unclear whether leflunomide inhibits LKB1-inactivated tumors in vivo, and whether its inhibitory effect on the immune system will promote tumor growth. Here, we carried out a comprehensive analysis of leflunomide treatment in various LKB1-inactivated murine xenografts, patient-derived xenografts, and genetically engineered mouse models. We also generated a mouse tumor-derived cancer cell line, WRJ388, that could metastasize to the lung within a month after subcutaneous im

SUBMITTER: Jin R 

PROVIDER: S-EPMC7867620 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature