By Robert Hazen, George Mason University
Cancer is a disease that’s going to strike more than a million Americans every year. The great irony of cancer is that it results from the fact that certain cells lose the ability to die. They forget how to die. It’s only recently that scientists have begun to understand the fundamental difference between a normal and a cancer cell. What is it?
A Cell’s Life Cycle
A normal cell ages and dies, as it has regulation mechanisms that keep track of the its life cycle. But a cancer cell is immortal because its internal clock is either turned off, or constantly reset, or sometimes, just ignored. The death of cells is driven by an extraordinary property of cells, that is, its ability to recognize internal damage.
If there’s been a mistake in DNA duplication or if there are some extra chromosomes, one either fixes the damage or the cell dies. If the chromosomes aren’t successfully segregated when a cell divides, then the cell dies. Thus, at each transition, the cell stops to check to see if everything’s been done correctly, and if it hasn’t, the cell kills itself.
Checkpoints in a Cell
There are several stopping points along the life cycle of a cell. These are called checkpoints, and they serve as the essential guardians of life. The details of these cellular mechanisms remain largely unknown, but we do know that the checkpoint machinery spots a defect in the cycle, and then it stops and either fixes it, or causes the cell to die. That’s the key idea here: that damage and programmed cell death are intimately tied, as long as the cell machinery is intact.
Cancer, it turns out, is a disease of continued, unsupervised growth; it occurs when this fundamental guardianship fails. If the cell cycle continues unchecked, then the cells keep reproducing and keep reproducing and a tumor forms. The result can be a terribly damaged cell that, instead of dying, just keeps thriving, over and over again. Indeed, there can be profound damage to the genetic material in these cells, and in spite of that profound damage, the cells just keep reproducing.
This is a transcript from the video series The Joy of Science. Watch it now, on Wondrium.
Genetic Abnormalities and Cancer
Over the past several years, scientists have succeeded in identifying several specific genes whose proteins produce the checkpoint pathways. What we find is that if we have accumulated mutations in several of these genes, that can lead to the development of cancer. In other words, defective genes, which cause defective proteins, result in cancer.
There’s an important point here: no single genetic abnormality is sufficient to cause cancer. Rather, one has to have a whole handful of these genetic abnormalities; five or six different genes all have to be defective simultaneously for a cancer to develop. How can we get five or six genetic defects at once? It turns out that many of the associated changes can be acquired or accelerated by exposure to certain kinds of environmental stresses.
For example, the chemicals in cigarette smoke accelerate certain kinds of damage in our cells. Organic solvents, atmospheric pollutants—a bad diet, even—can cause acceleration of these genetic damages. The probability that any one single cell acquires the damage is very, very low; but remember, we have 100 trillion cells in our body, so there are lots of cells in which multiple hits may develop.
The Checkpoint Pathways
This situation is quite different for individuals who are born with certain genetic defects. Up to 10 percent, of the 1.1 million cancer victims that are diagnosed each year, have at least one hit already in this genetic pathway.
Because they carry that first hit, they’re much more likely to develop cancer, because every cell in their body is already one step along the path. These individuals can carry lifetime risks of 80 to 90 percent of developing cancer.
Remember, all aspects of the cell cycle, every checkpoint pathway, has to in some way be related to a gene. If these genes are defective, cancer can develop. In order to better understand these genes, imagine that one is trying to push the cell through its cycle of testing to make sure it’s okay.
We can think of this as like an accelerator and a brake in our car. Some genes, called oncogenes, act like accelerators that drive the cycle continuously forward. In tumor cells, these genes are inappropriately turned on all the time, and so they produce too much acceleration. It’s like having our accelerator stuck in our car; one just keeps pushing right on through the checkpoints.
Damaged, Mutated Gene Increase the Risk of Cancer
Other genes, called tumor suppressant genes, normally act as brakes, and they block the progress, stopping the cell at various points to be checked. If the brakes aren’t working, it is going to keep on moving through.
We have a third type of cancer-susceptibility gene that encodes products that are directly involved with the DNA repair process, or the proteins that participate in programmed cell death. If we no longer are able to kill the cell internally—which is, of course, done with proteins—then, once again, the cell just keeps on living, keeps on reproducing.
This has led Paul A. Marks, of the Memorial Sloan-Kettering Cancer Center, to give the following quote. He said, “Over the next few years, for every major cancer—breast, prostate, colon, lung, and ovarian, as well as many of the rarer forms—a damaged or mutated gene or genes will be identified, whose presence increases the risk for specific cancer or cancers.”
In other words, if we’re born with certain genetic defects, which are carried in every one of the 100 trillion cells in our body, we have a much higher chance of getting cancer.
Common Questions about Cancer Cells
A normal cell ages and dies as it has regulation mechanisms that keep track of the cell’s life cycle. But a cancer cell is immortal, because its internal clock’s either turned off, or constantly reset, or sometimes, just ignored.
No single genetic abnormality is sufficient to cause cancer. Rather, one has to have a whole handful of these genetic abnormalities; five or six different genes all have to be defective simultaneously for a cancer to develop.
Genes, called tumor suppressant genes, normally act as brakes, and they block the progress, stopping the cell at various points to be checked.
