Research ArticleCancer

Metabolic perturbations sensitize triple-negative breast cancers to apoptosis induced by BH3 mimetics

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Science Signaling  08 Jun 2021:
Vol. 14, Issue 686, eabc7405
DOI: 10.1126/scisignal.abc7405

Depleting adenine to prime for apoptosis

Triple-negative breast cancers (TNBCs) are notoriously difficult to treat. Daniels et al. identified a metabolic vulnerability in TNBC patient cells and cell lines that may create a therapeutic opportunity in patients. The authors searched for metabolism-perturbing small-molecule compounds that sensitized TNBC lines to apoptosis induced by BH3 mimetics that block antiapoptotic proteins. They found that inhibition of NAMPT, the rate-limiting enzyme of the NAD+ salvage pathway, and specifically the loss of adenine downstream of NAMPT inhibition primed TNBC cells for apoptotic death. The findings suggest that combining NAMPT inhibitors with BH3 mimetics might be effective in some patients with TNBC.

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