Cancer cells are able to sleep like a ‘bear in winter’ when a threat such as chemotherapy treatment attacks them, according to new research – which apparently uses the tactics some animals use (although long lost in humans) to survive through periods in which scarce resources are. .
Knowing exactly how can evade cancer and resist drug treatment is an important part of the job of defeating them at all times, and therefore understanding this hibernation behavior may play an important role in future research. Cancer can often return after being dormant or apparently disappearing for a few years after treatment.
Preclinical research on human colorectal cancer cells revealed that they were able to slow down to a low-maintenance, ‘drug-tolerant persistence’ (DTP) condition, which would help explain failures in therapy and relapse. of crops.
“The tumor acts like a whole organism that can go into a slow division and save energy to help it survive,” says researcher and surgeon Catherine O’Brien, of the Princess Margaret Cancer Center in Canada.
“There are examples of animals that are in a reversible and slow-dividing state to resist in difficult environments. It seems that cancer cells have co-opted the same state with art for their survival benefit.”
The collection of human colorectal cancer cells in a petri dish and the exposure of the cells to chemotherapy, the researchers observed that the colorectal cancer cells go into the same hibernation state in the same way as when chemotherapy drugs were present. The cells have stopped expanding, which means they need very few nutrients to stay alive.
These observations also fit a mathematical model where all cancer cells, and not a small subpopulation, have a ‘balanced ability to become DTPs’, suggesting that these survival strategies can be seen in all cancer cells.
Researchers have also used xenografts of colorectal cancer cells on different sets of mice. Once the mice developed tumors of certain sizes, researchers treated the mice with standard chemotherapy regimens. Scientists have observed negligible tumor growth in mice treated for an eight-week period. When the treatment was stopped, the growth of the tumor started again.
Cancer cells taken from the tumors after a regrowth period were then inoculated into different mice and treated again. The regrowth cells remained sensitive to treatments, and their growth stopped and started in the same way, findings similar to the cancer cells that are in a DTP state.
This DTP condition is very similar to a hibernation condition called embryonic diapause in which mouse embryos relapse as a kind of emergency survival mode. Embryonic slides allow many animals, including mice, to effectively interrupt the development of the embryo until the environmental conditions are more favorable.
Here, cancer cells have been found to do a similar trick. Another link between the DTP condition and the embryonic diapause is their dependence on a biological mechanism called autophagy, in which cells essentially eat themselves to find the food they need. Autophagy occurs naturally in the body as a way to clear up waste, but in this case, cancers use it to stay alive.
“We never really knew that cancer cells were like winter species,” says oncologist Aaron Schimmer, of the Princess Margaret Cancer Center. “This study also tells us how we should target these sleeping bears so that they do not fall into hibernation and wake up to return unexpectedly later.”
“I think it will be a major cause of drug resistance, and it will explain something we did not have a good understanding of before.”
By targeting and inhibiting the autophagy process, the researchers were able to break the hibernation (or DTP) condition and kill the cancer cells for good with chemotherapy. This could be one approach to tackling conventional cancer-resistant tumors in the future.
Scientists already know of several other ways in which cancer can hide in the body, so this new study contributes to an increasing body of evidence on how to adopt the cancer cells that offer the best resistance to current drugs and approaches.
“It gives us a unique therapeutic opportunity,” O’Brien says. ‘We need to target cancer cells while in this slow, vulnerable state before they contract the genetic mutations that offer drug resistance.
“It’s a new way of thinking about resistance to chemotherapy and how to overcome it.”
The research was published in Cell.