Studies suggest that cancer cells may avoid chemotherapy by becoming dormant

According to a new study, cancer cells can dodge chemotherapy when they enter a state similar to certain types of aging. This is a type of “active hibernation” that allows you to survive the stress caused by aggressive treatments aimed at destroying cancer cells.

This study was led by scientists at Weill Cornell Medicine. These findings will influence the development of new drug combinations that may prevent aging and make chemotherapy more effective.

In a study published January 26 in Cancer Discovery, a journal of the American Association for Cancer Research, researchers may find this biological process useful in explaining why cancer recurs so often after treatment. I reported that there is. The study was conducted on both organoid and mouse models made from samples of patients with acute myeloid leukemia (AML) tumors. The findings were also validated by examining samples from AML patients collected during the course of treatment and recurrence.

“Acute myeloid leukemia can be relieved with chemotherapy, but most often it recurs and becomes incurable when cured,” said Sandra and Edward, professor of hematology and oncology at Gebroe. Meyer Cancer Center. “A long-standing question in this area was,’Why can’t you get rid of all the cancer cells?'” Similar questions can be raised in many other types of invasive cancers in addition to AML. “

For years, cancer researchers have been studying how tumors can rebound after appearing to have been completely wiped out by chemotherapy. One theory is that not all cells in a tumor are the same at the genetic level (a condition called tumor heterogeneity), so a small subset of cells can resist treatment and begin to grow again. .. Another theory includes the idea of ​​tumor stem cells. Some of the cells in a tumor have special properties that allow it to reshape the tumor after chemotherapy has been given.

The idea that aging is involved does not replace these other theories. In fact, it may provide new insights to explain these other processes, Dr. Merrick said.

The study found that when AML cells were exposed to chemotherapy, a subset of the cells became hibernating or aging, and at the same time very similar to inflammation. They resembled cells that were damaged and needed to promote wound healing-shut down most of their function while mobilizing immune cells to restore health.

“These characteristics are also common in the development of embryos that temporarily stop growing due to malnutrition, a condition called embryo dormancy,” explained Dr. Merrick. “This is not a special process, but it is a normal biological activity that occurs in a tumor situation.”

Further studies have revealed that this inflammatory aging condition is induced by a protein called ATR, suggesting that blocking ATR may be a way to prevent cancer cells from taking this condition. .. Researchers have tested this hypothesis in the lab, and giving leukemia cells an ATR inhibitor before chemotherapy can prevent the leukemia cells from aging, which can kill all cells with chemotherapy. I confirmed.

Importantly, studies published simultaneously by two other groups reported that the role of aging is important not only for AML, but also for recurrent cases of breast, prostate, and gastrointestinal cancer. I will. Dr. Melnick contributed to one of these other studies.

Dr. Melnick and his colleagues are currently working with companies that manufacture ATR inhibitors to find ways to reflect these findings in the clinic. However, more research is needed because many questions remain about when and how ATR inhibitors should be administered.

“Timing will be very important,” he said. “Before studying this in patients, we still have a lot to solve in the lab.”

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