TNBC tumours usually lack the molecular markers needed for many targeted therapies, so chemotherapy is the main option. PARP inhibitors work well only when tumours cannot perform homologous recombination (HR), but most TNBC tumours are HR‑proficient, limiting the drugs’ benefit.

The team discovered that Smyca binds the transcription factor FOXM1. This partnership directs FOXM1 to turn on genes that drive HR and nucleotide‑metabolism pathways, providing the building blocks and repair machinery cancer cells need after DNA‑damaging therapy.

When Smyca was blocked in HR‑proficient TNBC cells, in patient‑derived organoids and in mouse models, the cancers became far more sensitive to both chemotherapy and PARP inhibitors. The loss of Smyca also triggered the cGAS/STING pathway, an immune‑sensing system that can alert and recruit immune cells to attack the tumour.

"What makes this finding particularly important is that Smyca appears to connect two major mechanisms that allow tumours to survive from therapy, that is, DNA repair and immune escape," said Ruey‑Hwa Chen, a professor at the Institute of Biological Chemistry, Academia Sinica and Institute of Biochemical Sciences at National Taiwan University.

By targeting Smyca, doctors might weaken a tumour’s ability to fix treatment‑induced DNA damage while simultaneously exposing it to immune surveillance, potentially extending the use of PARP inhibitors to a larger group of TNBC patients.

The study, published in the Journal of Biomedical Science, suggests that interfering with this single RNA could turn a resistant cancer into one that responds to both targeted drugs and the body’s own defenses.