Cancer cells can avoid chemotherapy by entering a state that resembles certain types of senescence, a kind of “hibernation” that allows them to overcome the stress caused by aggressive treatments aimed at destroyed, according to a new study.
The study was led by scientists at Weill Cornell Medicine. These decisions have influenced the development of new drug combinations that can prevent senescence and make chemotherapy more effective.
In a study published Jan. 26 in Cancer Discovery, a journal of the American Society for Cancer Research, the researchers reported that this biological process may help explain why cancers are so common. recovery after treatment. The research was conducted in both organoids and mouse models made from patient samples of acute myeloid leukemia (AML) tumors. The findings were also confirmed by looking at samples from AML patients collected during the course of treatment and redistribution.
“Acute myeloid leukemia can be treated with chemotherapy, but it almost always comes back, and when it does it is impossible,” said lead author Dr. Ari M. Melnick , Gebroe Family Professor of Hematology and Medical Oncology and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “There has long been a question in the field, ‘Why don’t you get rid of all the cancer cells?’ A similar question can be asked for many other types of invasive cancer besides AML. “
For years, cancer researchers have studied how tumors can recur after appearing to have been completely eradicated with chemotherapy. One theory has been that since not all cells within a tumor have the same genetic level – a condition known as tumor heterogeneity – a small subset of cells is able to resist treatment and initiation. growing again. Another theory introduces the idea of tumor stem cells – that some of the cells inside a tumor have certain properties that allow a tumor to regenerate after chemotherapy.
The idea that senescence is involved does not replace these other theories. In fact, it could provide a new perspective on explaining these other processes, Dr. Melnick said.
In the study, the researchers found that when AML cells were exposed to chemotherapy, a subset of the cells entered a hibernation state, or senescence, while simultaneously assuming a condition that it looked a lot like swelling. They looked like cells that had been injured and needed to promote wound healing – shutting down most of their functions while recruiting immune cells to nurse them back. to health.
“These traits are also commonly seen in the development of embryos that close their growth over time due to malnutrition, a state known as embryonic diapause,” Dr. Melnick explained. “It’s not a specific process, but a normal biological activity that plays out in the context of tumors.”
Further research showed that this senescent inflammatory state was induced by a protein called ATR, suggesting that inhibition of ATR may be a means of preventing cancer cells from accepting this condition. The researchers tested this idea in the laboratory and found that administering ATR inhibitors to leukemia cells before chemotherapy stopped them from entering senescence, thus allowing chemotherapy to kill all the cells.
Importantly, simultaneously published studies from two other groups reported that the role of senescence is important not only for AML, but for recurrent cases of breast cancer, prostate cancer and gastrointestinal cancers. Dr Melnick contributed to one of these other studies.
Dr. Melnick and his colleagues are now working with companies that make ATR protectors to find a way to translate these findings into the clinic. However, much more research is needed, as there are still many questions about when and how ATR protectors need to be administered.
“Time will be very important,” he said. “We still have a lot to work out in the laboratory before we can study this in patients.”
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This story was published from a wire group group with no text changes.