Image: apoptoic cell death
The cells that make up the human body are good at stuff, demonstrating a kind of encoded/programmed intellect. One of the best examples may be a process known as autophagy, in which a cell isolates and decomposes relatively unnecessary parts of itself in order to provide additional energy or protein that can be used in times of nutrient scarcity or stress. Imagine being able to swallow your tonsils to replace a missed meal, or coughing up a kidney to be lightly seasoned and grilled. Research results have suggested that by reducing caloric intank and thereby inducing autophagy in animal cells, it may be possible to extend lifespans as the metabolic stress incurred by cells is reduced.
But it's not that easy. Autophagy is a pretty neat and helpful process, whether it's reducing by cell stress or ushering in programmed cell death, but the picture becomes complicated when we're talking about cancer cells. There's a large pool of ideas about how the process inhibits cancer—by removing bad or broken junk material from cells, or reducing chronic inflammation and necrosis—but at the root of things, autophagy is something that supports and enables the thriving of cells. And, as a fundamental cellular process, it doesn't appear to discriminate against tumor cells.
A study out this weekend from the University of Colorado demonstrates that this process of cellular recycling may be working against chemotherapy treatments in cancer patients, effectively allowing tumor cells to return from the dead. You can see it happen in the video above. At the start of the clip, mitochondrial cells walls begin to break down and the mitochondria themselves starting kicking out proteins, a stage of cell death known as MOMP (mitochondrial outer membrane permeabilization). MOMP should be the point of no return for the cell, as this stage begins a number of different signal cascades welcoming self-destruction via apoptosis, e.g. the "good" kind of cell death, in contrast to necrosis.
With MOMP underway, it should be hopeless for the cell. But what the CU team found is that in periods of elevated autophagy, the cell is able to recover by capturing those mitochondrial proteins and turning them back into useful stuff. The cell goes on to reproduce and thrive, which is bad news if that cell happens to be cancerous. "The implication here is that if you inhibit autophagy you'd make this less likely to happen, i.e. when you kill cancer cells they would stay dead," said Andrew Thorburn, deputy director of the CU Cancer Center.
So, we're left with a sort of conundrum. Autophagy is a necessary and good thing, and as chemotherapy acts to kill off cancer cells, it should work to the body's benefit, enabling those dying cells to not go to waste. The alternative to that sort of cell death is necrosis, which is what happens when a cell dies out-of-control and instead of being recycled. All that cell junk just builds up and rots, inviting infection and inflammation. This is what gangrene is.
The drug selected by the CU research team is known as TRAIL, and it's known to kill cancer cells by inducing apoptosis rather than necrosis. "Many chemo therapies also can kill by necrosis and we don't know if we would skew the death mechanism [toward necrosis] by inhibiting autophagy," Thorburn explained. "With TRAIL it doesn't seem so. We just get more tumor cell death by increasing apoptosis. However if it happened with other drugs it could be a good thing because there may be benefits to getting a more necrotic type of death."
Indeed, necrotic tissue induced by chemotherapy has been demonstrated to be a positive sign prognosis-wise in some patients. It may not be as pretty as programmed cell death, but you might say that a dead cancer cell by any means is a positive thing. And if that cancer cell happens to be back from the dead? Well, blow its brains out.