Today’s cancer drugs are more sophisticated and accessible than ever before. But unfortunately, cancer drug resistance remains a life-threatening challenge for patients and cancer care providers. In cancer treatment, drug resistance is often characterized by elusive tumor cells — cells which may initially respond to treatment but then gradually evolve resistance over the course of months or years. These cells may come back later in deadly force, contributing to patient death.
New research from the University of California San Diego (UCSD) delves into the mechanisms that drive and protect these elusive cells. The research successfully identified a unique survival strategy employed by these cells: co-opting an enzyme that is normally active only during cell death. Read on for what this research means for cancer treatment.
The Sneaky Enzyme Supporting “Persister” Cancer Cells
As mentioned above, some tumors are able to “escape” during cancer treatment, returning after therapy has concluded. Unfortunately, scientists aren’t sure why. In an attempt to understand this cellular behavior, the UCSD researchers investigated the “continual tumour evolution and multiple co-occurring resistance mechanisms” often observed in recurring cancer. The findings, which focused largely on oncogene-targeted cancer therapies, were published in Nature Cell Biology in November 2025.
How “Persister” Cells Linger Post-Treatment
The study focuses on a small population of cancer cells, known as “persister cells,” in models of skin, lung, and breast cancers. The researchers found that these cells can remain dormant during cancer treatment due to a sly mechanism: the activation of the body’s interferon signaling, which halts their growth. Persister cells have been found to use part of the cell’s own death machinery to ensure that they are able to resume growth after treatment. This process involves an enzyme called DNA fragmentation factor B (DFFB). As DFFB triggers DNA damage, it activates stress response pathways and ultimately suppresses interferon responses. The suppression is enough for some persister cells to begin regrowing. In essence, DFFB helps cancer cells fly under the radar during cancer therapy. They enter a “persister” state where they stop growing temporarily, only resuming growth after therapy concludes.
Targeting Stubborn Cancer Cells
This work suggests that targeting DFFB during cancer treatment could improve long-term treatment outcomes. “Rather than treating resistance after it emerges, it may be possible to prevent it by inhibiting the adaptive processes that initiate resistance,” the authors write in the study. Additionally, they note that DFFB is not required in normal cells, which makes it a promising target for low-side-effect therapies.
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“This flips our understanding of cancer cell death on its head,” said senior author Matthew J. Hangauer, Ph.D., in a UCSD press release. “Cancer cells which survive initial drug treatment experience sublethal cell death signaling which, instead of killing the cell, actually helps the cancer regrow. If we block this death signaling within these surviving cells, we can potentially stop tumors from relapsing during therapy.”
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