Investigation of 6-thioguanine as a strategy to overcome methotrexate resistance in a mouse model of leptomeningeal carcinomatosis.

ABSTRACT:

Purpose

Leptomeningeal carcinomatosis (LC), the dissemination of malignant cells into the cerebrospinal fluid, occurs in 3-5% of patients with solid tumors and is being recognized more frequently due to prolonged survival with systemic therapies. The prognosis remains dismal, with a median survival of 4-8 weeks. Methotrexate (MTX), the current standard treatment, is often compromised by resistance through dihydrofolate reductase (DHFR) upregulation and by neurotoxicity at high doses, underscoring the need for alternative therapeutic approaches.

Methods

An MTX-resistant subline (R-MM46) was established from a murine mammary carcinoma. Resistance was confirmed by increased DHFR activity, enhanced drug efflux, and apoptosis resistance, and validated in an LC mouse model. Metabo

SUBMITTER: Nakagawa H 

PROVIDER: S-EPMC12583346 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature