New cancer treatments may be revealed in genes
Kent Hunter searches for genes that suppress cancer’s spread.
Kent Hunter is a geneticist at the National Cancer Institute in Maryland. For nearly a decade, he has been looking for versions of genes that suppress cancer metastasis. Earth & Sky’s Marc Airhart spoke with him about his research.
Airhart: How is the science of genetics linked to cancer research?
Hunter: Everyone has different versions of the same genes. So, just as people are different heights or have different color hair or eyes, these variations in the genes can control or influence many different aspects of biology, including cancer. We’re trying to identify which of these genes have variances in them that either make them more or less likely to enable cancer to spread. And if we can identify what those genes are, then hopefully they might be able to lead us to better therapies or even better preventions to keep the cancers localized.
Airhart: If cancer is found where it started, it’s more treatable?
Hunter: Yes. If the cancer stays localized, there’s a much better chance that you can just go in and just remove it surgically. And if you can keep it localized and it’s surgically accessible, then the patient’s chances are much better than if the cancer is spread already.
Airhart: So, you study mice to look at the genetics of how cancers spread. Can you tell me more about that? How many mice are we talking and how long do the experiments take?
Hunter: Well there are a number of reasons we use mice. One is we can do genetic experiments that we can’t do in people. We obviously can’t tell people who to have children with and things like that. You can manipulate mice. We can do experiments on them, and control their environment: what they’re exposed to, what they eat. Their lifespan is considerably shorter than humans. And for whatever reason that is not completely understood, the course of their cancers is also faster.
So, just as their lifespan is accelerated, the diseases of aging, of which cancer is one, is also accelerated. That means the time frame in which we can operate is much faster. And although mice are obviously not people, they share many of the biological and physiological functions that we do. They’re not perfect models, but they’re ones that are relatively easy to use and manipulate, where we think we can get some idea of what we think is happening in the humans. Later, we would do experiments in humans to see whether what we’ve seen in mice is occurring humans as well.
Airhart: At what stage is your research now?
Hunter: That’s a good question. We’re always kind of in the middle of the studies.
We think we may have some idea of what some of the genes asscoaited with the spread of cancer are. There are probably very many of these genes, of which we’re only looking at a few that our particular model system enables us to see.
We’re doing a lot of work trying to figure out whether we can use this information to — at least in the experimental animals and, if it works there, hopefully in people — predict which animals in a population are most likely to have the cancer spread.
And if we can actually do that we’re hoping we may be able to use the information that we develop to find some ways of actually, pharmacologically, preventing the metastases from forming. I mean at least the secondary tumors that are actually causing the problems.
So, we’re in the middle of all that. And this is kind of a cyclical process. We’ll be doing this kind of work probably for the rest of my career and maybe for many other people’s careers as well as we continue to refine our knowledge and what we can do about the spread of cancer.
Airhart: Tell me more about how the experiments are done.
Hunter: The experiment is done as follows. We started out with a mouse that had been engineered to develop a cancer. This particular model system we use has a very high degree of metastasis. Suppose we call this original strain, witih the metastatic tumor, strain A..” If you take a strain B and you mate strain A to strain B — so the children are now half A and half B — we’ll call them AB’s. The AB’s will have a different level of metastases than strain A does because of the introduction of the gene variance from strain B. So you can use that information to then use those two strains, A and B, to set up an experimental genetic cross to map what genes in strain B are causing the suppression of metastasis. You can then look at those genes and see what’s different about them in strain A and strain B and hopefully that gives you some information about what’s changing the metastatic process from one strain to the other. Hopefully, we know enough to understand how that’s happening. If we don’t, we have to figure out why it’s happening.
Airhart: So, why is it necessary to go through all those steps to create a range of strains, when you could simply compare the strain that doesn’t have metastasis to the strain that does? Do they just differ so much that it’s too hard to study all the differences?
Hunter: Yes, that’s right. There’s about as much DNA in a mouse as there is in a human. That’s about 3 billion base pairs of DNA. And that’s at least 20,000 to 30,000 genes, maybe more.
And when you actually sit down and compare that much DNA to each other, we simply can’t do it. We don’t have all of these inbred strains completely sequenced. And we may never have them all completely sequenced. And, even if you could directly compare the sequences, that doesn’t necessarily tell you what changes are important or not. There are going to be thousands or millions of changes between inbred strains of mice and just knowing that they’re there doesn’t help you figure out what’s actually important at the biology level.
Airhart: What’s the ultimate goal of this work?
Hunter: I’m hoping that what we’ll be able to do is improve individualized medicine. Now, for example, we would consider a population of people that have breast cancer. And you treat them in some way that you improve survival for some percentage of them. What we’d like to do for medicine is identify people who would respond to drugs better or identify what drugs people will respond to. Then, if a woman comes in with breast cancer, we can say, We know you won’t respond to this drug, so we’ll put you on this other drug that you will respond to.” And that just improves our ability to treat patients individually.
I’m interested in trying to help clinicians deal with the problem of cancer metastasis. Either they’ll use the information that we find to design better drugs that will do a better job of killing the metastases, or they’ll design drugs that will prevent certain people who are likely to get metastases from getting the secondary tumors at all. If we can prevent that, then these people are going to live a much longer and a much happier life than they would going through these multiple rounds of therapy needed to try to kill the disseminated disease.
There are still a significant number of people who come into the clinics, who the clinicians think have a localized disease that has not spread. These people are operated on, and the tumors are removed. But five years later, even though the clinicians could not detect cells that had spread to some other part of the body, those patients are back in the clinic because they have metastases. If we can identify those people when they come in the first time, we could say, Okay, it looks like you have a localized tumor. And, based on your genetic profile, you’re at high risk for metastases.” Then we’d like to be able to put them on some sort of drug that will either kill those disseminated cells before they become metastases, or prevent those cells from ever growing to become metastases.
It’s a prevention regime much like people at risk for heart disease are being told to take baby aspirin. If we can do something like that, then we’re going to reduce cancer mortality and improve these patients quality of life by simply reducing or eliminating having to go back in and undergo secondary rounds of chemotherapy or surgery in order to get rid of these secondary tumors that come up years later.
Airhart: Dr. Hunter, we appreciate your speaking with Earth & Sky.
