Scientists Discover Why Some Breast Cancer Cells Refuse to Die
New Delhi, November 26 — In a breakthrough that could change how doctors treat one of India’s most challenging cancers, researchers have uncovered the secret survival tactics of stubborn breast cancer cells that resist chemotherapy.
A team at the Tata Memorial Centre’s Advanced Centre for Treatment, Research, and Education in Cancer (TMC-ACTREC) has been investigating triple-negative breast cancer (TNBC), which accounts for nearly a third of all breast cancer cases in India. What makes this cancer particularly dangerous is its resistance to standard treatments.
Dr. Nandini Verma, the principal investigator from the Cancer Research Institute (CRI) division of TMC-ACTREC, explains that while chemotherapy initially kills most cancer cells, some manage to survive by entering a kind of hibernation. “They’re in a temporary dormant state,” she says. These sleeping cells later wake up, multiply aggressively, and spread the cancer throughout the body.
Understanding the Enemy
Triple-negative breast cancer gets its name from lacking three key receptors estrogen, progesterone, and HER2 that doctors typically target with therapies. This means more than 70% of breast cancer patients have treatment options, but those with TNBC can only receive combination chemotherapy.
The problem is that even when chemotherapy appears to work initially, about half of patients experience relapse. The cancer comes back more aggressive than before, often spreading to the lungs, liver, and brain.
The research team has now identified the molecular mechanisms that allow these resilient cancer cells to persist and later become more dangerous. Their findings appear in the November issue of Redox Biology.
The Molecular Shield
The scientists focused on cancer cells that have evolved what they call “Drug-Tolerant Persisters” (DTPs) — cells that can sense when chemotherapy is coming and essentially hide until the danger passes. Once treatment stops, these cells transform into highly aggressive tumors.
Two molecules, GPX4 and FSPN1, play crucial roles in making cancer cells resistant to chemotherapy. The researchers found that blocking FSPN1 can restore the cells’ vulnerability to treatment.
They’ve demonstrated how to flip a cellular switch that changes cancer cells from “chemo resistant” to “chemo sensitive” by targeting FSPN1’s protective mechanism. This therapy uses a powerful combination that blocks both GPX4 and FSPN1, essentially breaking down the cancer cells’ defensive barriers by damaging their membranes.
What This Means for Patients
For patients who fail to achieve complete remission, this research offers new hope. Managing those who experience disease recurrence has been particularly challenging due to limited understanding of why some cancer cells survive treatment.
