Scientists at the Tata Memorial Centre – Advanced Centre for Treatment, Research, and Education in Cancer (TMC-ACTREC) – have identified a crucial vulnerability in triple-negative breast cancer (TNBC).
It is a highly aggressive form of the disease that accounts for nearly 31 per cent of breast cancer cases in India.
The discovery, published in the November issue of Redox Biology, could pave the way for more effective therapies against tumours that stop responding to chemotherapy.
TNBC lacks the estrogen, progesterone, and HER2 receptors that enable targeted treatments for most breast cancer patients. As a result, chemotherapy remains the only standard option.
While many patients initially respond, nearly half relapse if residual disease remains after treatment. These recurring tumours are notoriously aggressive and spread rapidly to major organs.
Current challenges stem from a small group of cells that survive chemotherapy by temporarily entering a dormant state, only to reactivate and become drug-resistant.
The new study closely examined these survivors, known as drug-tolerant persisters (DTPs). Researchers mapped how these cells shut down their growth to withstand chemotherapy and later transition into highly aggressive cells that drive recurrence. This molecular mapping revealed the triggers that enable them to persist.
The team identified two molecules — GPX4 and FSP1 — that act as shields, allowing TNBC cells to escape chemotherapy-induced death. Blocking FSP1 alone made the resistant cells sensitive to treatment again. Building on this insight, researchers developed a combined therapy that targets both GPX4 and FSP1, effectively damaging the membranes of these tough cancer cells and killing them.
Dr. Nandini Verma, who led the study, said the findings mark an important step in understanding why TNBC relapses so frequently.
The discovery also has immediate clinical implications. Levels of GPX4 and FSP1 can serve as biomarkers to predict which patients may not respond well to chemotherapy, helping doctors intervene earlier. The combined therapy approach, if validated in human trials, could become a promising treatment strategy for eliminating drug-resistant tumour cells.
The researchers said the next phase will involve testing the therapy in clinical trials to determine whether it can prevent recurrence and improve long-term outcomes for patients with this challenging form of breast cancer.