According to a news release from the University Health Network last week, Dr. Catherine O'Brien and her team discovered cancer cells can cleverly enter into a restful state when threatened.
Tumor cells have developed the capabilities to thrive in harsh conditions by going into a sluggish dividing or dormant mode. Dr. Aaron Schimmer, Director of the Princess Margaret Cancer Centre Research Institute and Senior Scientist, states that this research indicates that cancer cells hibernate in winter, like wolves.
Princess Margaret Scientist Dr. Catherine O'Brien and team discovered in study reported in Cell on January 7, 2020 that while under attack, all cancer cells have the potential to migrate into this defensive state, where the cells rest before the threat or chemotherapy is eliminated, rather than only a subset.
It is the first research to establish that cancer cells are hijacking an innovative retained chemotherapy survival program. The researchers also demonstrate that in this slow-dividing state, innovative therapeutic techniques aimed directly at attacking cancer cells will avoid cancer regrowth.
Using actual colorectal cancer cells, the researchers treated them in a petri dish in the laboratory with chemotherapy.
This caused a slow-dividing condition that needed little nutrients to live in all the cancer cells in which they stopped spreading. The cancer cells persisted in this condition as long as the chemotherapy continued in the dish.
"Something clicked for me when I heard that talk," said O'Brien. "Could the cancer cells be hijacking this survival mechanism to survive chemotherapy?"
The cancer cells have co-opted an embryonic survival program utilized by over 100 species of mammals to maintain their embryos healthy within their bodies in periods of harsh environmental circumstances, such as high or low temperatures or lack of food, in order to reach this low-energy state.
There is reduced cell division in this condition, significantly diminished metabolism, and embryo production is placed on hold. The fetus is likely to begin normal growth as the climate changes, with no detrimental effects on the baby.
In the chemotherapy-induced, slow-dividing state, she contrasted the gene expression profile of the cancer cells to the paused mouse embryos in Dr. Ramalho-Santos' lab, and noticed that they were remarkably close.
Like embryos, cancer cells need activation of the cellular mechanism called autophagy in the slow-dividing state, meaning "self-devouring" This is a mechanism in which, in the absence of other foods, the cell "devours" or kills its own proteins or other cellular components to live.
A small molecule which inhibits autophagy was tested by Dr. O'Brien and found that the cancer cells did not live. The cancer cells were destroyed by chemotherapy without this defense mechanism.
Cover Photo: In the first of its kind research, Princess Margaret Scientist Dr. Catherine O'Brien identified an ancient, evolutionary survival mechanism co-opted by cancer cells to survive the harsh environment of chemotherapy. Credit: Visual Services, University Health Network