Cancer is extremely tricky to get rid of. Even after a successful therapy that has seemingly extinguished a tumor, cancer can return unexpectedly years later. According to a new study, this happens as a result of cancer cells entering a dormant state that allows them to evade destruction from chemotherapy. The same cellular process is employed by some hibernating animals in nature.
"We never actually knew that cancer cells were like hibernating bears,” Aaron Schimmer, a scientist at the Princess Margaret Cancer Centre in Toronto and co-author of the new study, said in a statement. “This study also tells us how to target these sleeping bears so they don't hibernate and wake up to come back later, unexpectedly.”
The team of researchers led by Dr. Catherine O'Brien, who is an Associate Professor in the Department of Surgery at the University of Toronto, studied human colorectal cancer cells that were treated with chemotherapy. The scientists observed that the chemotherapy induced the cells into a slow-dividing state.
Gene expression in these treated cancer cells was found to closely resemble that of rodent embryos when they shift to a hibernation-like state known as embryonic diapause. This survival mechanism is used by more than 100 species of mammals in nature to keep their embryos safe during times of extreme environmental conditions, such as freezing winters or lack of food.
During embryonic diapause, cell division is minimal, thus reducing energy expenditure and greatly reducing metabolism. This slow-dividing state requires the activation of a cellular process called autophagy ("self-devouring"), a process in which the cell literally consumes its own proteins or other cellular components in order to survive the absence of other nutrients. Once environmental conditions improve, the embryo resumes normal development with no adverse effects on pregnancy.
Essentially, the cancer cells have hijacked this embryonic survival strategy, enabling them to withstand the onslaught of chemotherapy, even though humans themselves seem to have lost this ability. All cancer cells enter this state in a coordinated manner, the researchers reported in their study published in the journal Cell.
Understanding how exactly cancer cells resurface even after successful therapies may be key to preventing relapses. When the researchers employed a molecule known to inhibit autophagy, they found that cancer cells no longer survived when subjected to chemotherapy.
"This gives us a unique therapeutic opportunity," says Dr. O'Brien. "We need to target cancer cells while they are in this slow-cycling, vulnerable state before they acquire the genetic mutations that drive drug-resistance.
"It is a new way to think about resistance to chemotherapy and how to overcome it."