Latest findings and understanding of “zombie cancer” behavior in cells may help oncologists and cancer researchers to better treat tumors and cancer patients. On April 5, 2014 at the American Association for Cancer Research (AACR) Annual Conference, a study from the University of Colorado Cancer Center that was published in Cell Reports showed that some cancer cells ‘eat’ parts of themselves to survive, hence the nickname “zombie cancer cells.” When these cells undergo stress, they divide to recover instead of dying when they are attacked by chemotherapy treatments. While this process may not cause patients to come back from the dead, it complicates treatments and baffles physicians and researchers.
Nearly all cells undergo a cell cycle where they reproduce by mitosis and meiosis and die by apoptosis, in which the process eliminates all traces of the cells. They do so by undergoing autophagy, eating parts of itself that are no longer functional and controlling the process of apoptosis. Cells isolate and break down these waste materials, which are turned into energy, allowing other healthy cells to survive. If the natural process of cell cycle does not occur, then tumors can form. However, the recent study showed that autophagy could bring tumor cells back to “life.”
While working on a cancer drug called “TRAIL,” researchers observed that when the walls of the tumor cells’ mitochondria — the energy-generating powerhouses of the cells — broke down, a high level of autophagy started to scavenge and reassemble pieces of the cells’ part and restore their functions, even to the point of dividing and reproducing. Andrew Thorburn, Ph.D., deputy director of the University of Colorado Cancer Center, stated that when the levels of autophagy is too high or is not regulated, cancer cells are more likely to “rescue themselves from death caused by chemotherapies.” Rather than directing treatments to kill cancer cells, a better option may be to inhibit the triggers for excessive autophagy.
When cells die, a protein called MOMP is released, which is common indicator of cell death. A high level of autophagy, however, allows the zombie cancer cells themselves to trap and “eat” these proteins before MOMP can reduce their chances of survival and keep them dead. Thorburn and his colleagues said that autophagy depends on a protein called p53 upregulated modulator of apoptosis, or PUMA. When PUMA isn’t around to regulate, autophagy is not very likely to be inhibited, which allows cancer cells to thrive and survive. The researchers removed PUMA to prove this theory and the result showed that autophagy can “zombify” cells by destroying waste materials and create “new” cells with whatever protein fragments it could find.
Although Thorburn suggests that killing cancer cells by necrosis — the process of killing cells artificially by radiation or depriving them of nutrients — rather than a programmed process like apoptosis, necrosis has its drawbacks. When cells die by necrosis, they aren’t recycled like in apoptosis. These materials end up as garbage in the body that proliferates and rots, leading to gangrene.
The idea that cancer cells can eat themselves to survive sounds like an episode of The Walking Dead, but this phenomenon won’t instigate a zombie apocalypse. “Autophagy is complex and as yet not fully understood,” Thorburn said. He noted that better understandings of cells functions and mechanisms can lead to more answers to treating specific cancers in certain populations.
By Nick Ng