Cell's unexpected new discovery: It turns out that this "near-death experience" makes cancer cells worse

Scientists at St.

The findings were published in the journal Cell

After treatment, cancer sometimes comes back, and researchers know that a small subset of cancer cells can sometimes develop drug resistance that persists after treatment

Corresponding author Doug Green, PhD, Chair of the Department of Immunology, said: "For cancer cells, nothing that kills them makes them stronger

near-death experience

Many drugs used to treat cancer trigger apoptosis

The team showed in the laboratory that these persistent cells did indeed begin to die, and that this near-death experience was key to their survival

"This persistence phenomenon is caused by a 'near-death experience' that engages the mitochondrial apoptotic pathway without dying," Green said

Simultaneous promotion of survival and inhibition of apoptosis may also explain why persistent cells develop resistance to treatments other than the original drugs used to treat cancer

potential drug targets

The research could provide the basis for drugs that prevent cancer recurrence by interfering with a key protein in the stress response

In persistent cells, the stress response leads to an increase in the intracellular protein activating transcription factor 4 (ATF4)

The team found that genes regulated by ATF4 in their persisting cells were similarly regulated in cancer cells from patients who survived chemotherapy, suggesting that this process occurs during cancer treatment

continuing pattern

The researchers came up with a model for how persisters could be formed

article title

Sublethal cytochrome c release generates drug-tolerant persister cells