Targeting fatty acid synthase to overcome PARP inhibitor resistance and to create an artificial synthetic lethality for triple-negative breast cancer.

ABSTRACT: Despite advances in cancer treatment with targeted therapies and immunotherapies, triple-negative breast cancer (TNBC) has not significantly benefited from these developments. Although poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for breast cancer, their clinical use is largely limited to the small subset of HER2-negative patients with germline BRCA1/2 mutations, and resistance is frequently observed. Previously, we demonstrated that proton pump inhibitors (PPIs), including lansoprazole and its metabolite, 5-hydroxy lansoprazole sulfide (5HLS), reduce PARP1 expression by inhibiting fatty acid synthase (FASN), a key enzyme in de-novo lipid synthesis. We also found that PPIs synergize with DNA-damaging agents by regulating PARP1 expression and impairing n

SUBMITTER: Josephraj S 

PROVIDER: S-EPMC12557586 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature