Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases.

ABSTRACT: A paucity of chemotherapeutic options for metastatic brain cancer limits patient survival and portends poor clinical outcomes. Using a CNS small-molecule inhibitor library of 320 agents known to be blood-brain barrier permeable and approved by the FDA, we interrogated breast cancer brain metastasis vulnerabilities to identify an effective agent. Metixene, an antiparkinsonian drug, was identified as a top therapeutic agent that was capable of decreasing cellular viability and inducing cell death across different metastatic breast cancer subtypes. This agent significantly reduced mammary tumor size in orthotopic xenograft assays and improved survival in an intracardiac model of multiorgan site metastases. Metixene further extended survival in mice bearing intracranial xenografts and in an in

SUBMITTER: Fares J 

PROVIDER: S-EPMC10721147 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature