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Hibernation – how cancer cells utilise strategies

Treatment of cancer can be split into two different categories – targeting and destroy rapidly dividing cells via chemo or radiotherapy, or target cells expressing cancer markers via immunotherapy.

Hibernation – how cancer cells utilise strategies used by mice and bears to survive

 

Treatment of cancer can be split into two different categories – targeting and destroy rapidly dividing cells via chemo or radiotherapy, or target cells expressing cancer markers via immunotherapy. During treatment, the efficacy of chemo, radio or immunotherapy can be determined by looking at cancer biomarkers in the blood, or by re-scanning the patient to look at cancer activity. A reduction in these markers can give us assurances that the cancer is being treated, but this isn’t always the case. Recurrence or relapse is always an issue, and it is something we do not understand well.

Research so far has revealed that different types of cancer use different techniques to achieve dormancy and hide from the immune system. Some hide in fatty tissue, others achieve an equilibrium with the body’s immune system. Breast cancer cells have been found to undergo dormancy when exposed to some medications. This is similar to the hibernation state found in animals, and this is not just an apt metaphor.

The experiment looked at human colorectal cancer cells treated with chemotherapy. When exposed to chemotherapy agents, cancer cells were induced into a slow dividing state, able to survive with little nutrition. The gene expression of this state closely resembled that of mouse embryos when they undergo embryonic hibernation.

This embryonic hibernation is seen in over 100 types of mammals and is usually triggered when the mother is exposed to unfavourable environments when pregnant. Embryonic development is paused until a time when conditions become more favourable for pregnancy and birth. When entering hibernation, embryos undergo a cellular process called autophagy – where the cells essentially devour proteins inside the cell to survive. This same process was found in the dormant cancer cells, and when the autophagy mechanism was inhibited, the cancer cells failed to remain dormant and were ultimately destroyed by the chemotherapy.

This gives an interesting insight into how cancer cells utilise evolutionary strategy found in other mammals, intrinsic to our cellular makeup but not utilised by humans during reproduction, pregnancy or birth. Yet this conserved strategy provides cancer cells with another defence mechanism to survive against destruction by modern medicine. Understanding these mechanisms is key to improving the efficacy of our oncological treatment.

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