Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

ABSTRACT: Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib. Conversely, inhibition of VLCFA degradation via suppression of peroxisomal acyl-CoA oxidase 1 (ACOX1) increased the cytotoxicity of bortezomib, its next-generation analog, carfilzomib, and the immunomodulatory agent lenalidomide. Furthermore, treatment with an orally available ACOX1 inhibitor cooperated with bortezomib in suppressing the growth of bortezomib-resistant MM xenografts in mice. Increased VLCFA le

SUBMITTER: Han Z 

PROVIDER: S-EPMC12175649 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature