A near-death experience worsens some cancer cells

Scientists at St. Jude Children’s Research Hospital have identified how some cancer cells cheat treatment-induced cell death. In doing so, they persist and lead to cancer recurrence. The findings may serve as the basis for drugs that prevent relapses by inhibiting cancer cells from gaining these persistence traits. The research was published today in Cell.

After treatment, sometimes the cancer returns, called a recurrence. Researchers knew that a small population of cancer cells sometimes become drug resistant and persist after treatment. These “persister” cells can then reconstitute a more aggressive form of the same cancer. Until now it was unclear how these cells initially change to become persistent.

“When it comes to cancer cells, what doesn’t kill them makes them stronger,” said corresponding author Doug Green, Ph.D., Department of Immunology chair. “The field has begun to recognize that just because a cell engages apoptosis [a cell death pathway] doesn’t mean it will die. Our conceptual leap was that such ‘near death experiences’ could be responsible for the generation of persister cells. This was unexpected — it was like finding a piece of a treasure map that you never knew was missing — new paths to discovery have opened up.”

A near-death experience

Many drugs to treat cancer trigger apoptosis. St. Jude researchers found that a key event that leads to apoptosis, the release of the protein cytochrome c from mitochondria, occurs in persister cells. Historically, researchers believed that once cytochrome c was released into the cell, apoptosis could not be stopped. The evidence that some cells survive the process has grown, but it was unclear how, or why survival would lead to more aggressive cancer.

The St. Jude group showed in the lab that these persistor cells do start apoptosis and that this near-death experience is key to their survival.

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