Cancer cells hibernate like "bears in winter" to survive chemotherapy
Even after the most successful cancer treatment, doctors are reticent to use the word "cured". Different types of cancers have different rates of recurrence and many cancers can sit quietly, dormant for years, before reappearing and causing a relapse.
Understanding exactly how these cancer cells go dormant and hide for years is still a bit of a mystery for oncologists. Targeted research has revealed different types of cancer cells potentially utilize a variety of methods to achieve stasis, from hiding out in fatty tissue to reaching a novel equilibrium with the immune system. One study even found drugs used to treat breast cancer can directly trigger dormancy in some cancer cells.
A compelling new study, published in the journal Cell, is suggesting all cancer cells may have the capacity to enter states of dormancy as a survival mechanism to avoid destruction from chemotherapy. And the mechanism these cancer cells deploy notably resembles a process utilized by hibernating animals.
"The tumor is acting like a whole organism, able to go into a slow-dividing state, conserving energy to help it survive," explains Catherine O'Brien, corresponding author on the new study. "There are examples of animals entering into a reversible and slow-dividing state to withstand harsh environments. It appears that cancer cells have craftily co-opted this same state for their survival benefit."
The preclinical research was conducted on human colorectal cancer cells. In laboratory conditions the researchers discovered chemotherapy treatment seemed to induce the cells into a slow-dividing state. The gene expression of the cancer cells in this slow-dividing state was found to closely resemble that of mouse embryos when they shift to a hibernation-like state called embryonic diapause.
More than 100 mammals, from bears to mice, have the ability to undergo embryonic diapause. The mechanism is thought to be triggered by unfavorable environmental conditions, causing an organism to essentially pause an embryo’s development until conditions become more favorable for survival.
A key characteristic of embryonic diapause is a cellular process called autophagy. The new research discovered cancer cells utilize this same autophagy mechanism to enter a dormant state and evade destruction from chemotherapy. When autophagy was inhibited, the researchers found the cancer cells were unable to enter hibernation and were effectively killed by chemotherapy.
Aaron Schimmer, a scientist at the Princess Margaret Cancer Centre, describes this mechanism as similar to the way bears hibernate in winter. He also suggests understanding this mechanism offers great insight into why some people do not respond well to chemotherapy.
"We never actually knew that cancer cells were like hibernating bears,” says Schimmer. “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 study calls these hibernating cancer cells "drug-tolerant persisters" (DTPs), and the model produced by the researchers suggests all cancer cells have the capacity to become DTPs. O’Brien says this novel insight into how cancer cells evade death from chemotherapy points to exciting new potential cancer treatments designed to inhibit this hibernation-like mechanism.
"This gives us a unique therapeutic opportunity," says 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."
The new study was published in the journal Cell.
Source: University Health Network