Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion

Habib A Serhan; Liwei Bao; Xu Cheng; Zhaoping Qin; Chia-Jen Liu; Jason A Heth; Aaron M Udager; Matthew B Soellner; Sofia D Merajver; Aki Morikawa; Nathan M Merrill

doi:10.1038/s41523-024-00656-0

Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion

NPJ Breast Cancer. 2024 Jun 10;10(1):43. doi: 10.1038/s41523-024-00656-0.

Authors

Affiliations

¹ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
² Department of Neurosurgery, University of Michigan, Ann Arbor, MI, 48109, USA.
³ Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴ Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. [email protected].

Abstract

Fatty acid synthesis (FAS) has been shown to play a key role in the survival of brain-metastatic (BM) breast cancer. We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM cell lines, upregulates FAS and downregulates cell cycle progression gene expression, and slows the motility of TNBC BM cell lines. The combination of SN-38 and TVB-2640 warrants further consideration as a potential therapeutic option in TNBC BMs.

Abstract

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