Dr Judy Garber, Dana Farber Cancer Institute
At its heart, cancer is a disease caused by faulty and damaged genes. It’s usually a combination of the damage we pick up over a lifetime, as well as our own unique tapestry of genetic variation and - in some cases - specific gene faults that we inherit. To find out more about how faulty genes are involved in cancer, and how our understanding of them is helping to shape the cancer treatment of the future, I spoke to Dr Judy Garber from the Dana Farber Cancer Institute in Boston.
Judy - Well, it turns out that we have many genes in the body that have as their main job keeping the function of cells accurate and particularly making sure that when cells divide and make new cells that their genetic material is exactly the same as the parent cell, so that no mistakes are passed on. The genes that help make sure that cells can police themselves and make sure that they're correct are genes that must be functional for the cells to be accurate. When one of those genes doesn’t do its job, then it’s easier for mistakes to occur and for cancers to develop. So, the inherited piece of this is that in normal cells, we usually have two copies of each gene and both of them usually work just fine, but in people who have an inherited risk, one copy of the gene may not work so well. And usually, the cells are fine with just one working copy, but when something happens to knock out the working copy, some carcinogen exposure, radiation or chemicals, whatever it is that allows the normal copy to disappear, now the cell is more defenceless in that way and cancer can occur.
Kat - Now, what are some of the big hitters that we already know about, some of the genes that we know really do increase cancer risk if you inherit a dodgy copy?
Judy - Well, I think we’ve known for a long time that cancers can cluster in families. So we’ve known about the BRCA1 and BRCA2 genes that were found in the early ‘90s to explain a subset of breast cancer families. We know about a lot of genes that give familial risk of colon cancer and we probably don’t recognise as often as we should that some of those families also get too much uterine or endometrial cancer, cancer of the womb, and ovarian cancer. And then unfortunately, we know some cancer syndromes that affect children and that’s always the hardest, I think.
Kat - Now, what are we starting to discover about some, maybe less common or harder to find gene faults that are running in families and increasing cancer risk? What are the new things that are coming through?
Judy - So, I think it’s been easier to find genes to explain rare cancers and very powerful genes that give an enormous amount of risk and would make anyone wonder about a family. But now, we’re starting to find more information about genes that are a little less powerful and that are probably a little more common in the population. And we have a lot of work to do to be more exact about their effects on cancer. Some of these is happening because the technology has improved for analysing genes in general and so, we’re finding more changes in genes that we know have a role to play in cancers, and therefore, also apparently in cancer susceptibility or cancer risk.
Kat - Now, we hear a lot about how cancer treatment is moving towards personalised medicine, so you take a sample of a tumour, you do a genetic analysis, and you say, “OK, you need this drug and you need this drug.” How does that interplay on top of what might already be going on in someone’s cells, just the kind of gene profile they’ve inherited because they're them?
Judy - So, there are many ways for that to work. One way people expect to be an issue is that some of the changes in the tumours started out as changes in some people in their original genes, and the tumours that they get have a particular biology because of their contribution of that original gene, and you find it by looking at the tumour genetics and then saying, “Well, wait. Let’s look also at the person’s own genes and get rid of the ones that were abnormal to begin with.” So, that’s one possibility. The other is and that because we’re going to be looking at all these genes, we’re going to learn about genes that affect very basic things about drugs we’ve known all along like the metabolism of drugs. So, why is it that two people can take the same dose of a medication and one has side effects and the other does not? So, it’s probably nothing about the drug, but it may be the way the person handles that drug in their own body. And of course, that can be affected by lifestyle and other factors, but some of it is determined by genes that affect drug metabolism, so we should learn more about that too. Maybe that can help us avoid some side effects.
Kat - It’s seeming to me that cancer is now as unique as we are. An individual’s cancer is almost completely unique. That seems to me to present a huge challenge for doctors and scientists. What do you think are the challenges and how are we working to overcome them?
Judy - Well, I think that the challenges certainly are huge. Cancers are to some extent unique and they develop changes that are unique, but if they are using the same set of fundamental genes that drive them then hopefully, we’ll be able to group them just differently instead of thinking about breast cancer, lung cancer, prostate cancer we may be looking for a group of cancers that have a particular gene at their base and the fact that they occurred in a different tissue may not matter quite as much as we use to think. But this requires a huge amount of analysis and a lot of thinking and, unfortunately, that’s all pretty expensive, so there's some of that to contend with.
Kat - We’re entering an era now where's just a huge amount of data coming out from genome sequencing, these big cancer genome projects, and things like that. And even people themselves, you can pay maybe around $1,000, 1,000 pounds and have your own genome sequenced. How do we try and get the grips with this kind of information and then what might people do with it if they find they have a risky gene?
Judy - The first question I think is fortunately, the province of people who love big data sets and they're out there and that…
Kat - The computer nerds.
Judy - Those computer nerds, they’re finally going to really come in handy. And they can take this information and help sort through all of the noise to try to find the music, and I think that fortunately is what they're good at. The challenge will be to try to make the information available and to annotate it. And by that, I mean, that it’s not enough just to know your genes. You have to know about the clinical impact and so, you're going to need information about the tumours and response to treatment, and family history, and things to give you context to interpret all the rest. So that’s just more data, but I think that will be important.
Kat - And if someone say, has a test done either by a researcher, or pays for it, and then discovers they have a mutation, how do we know if it’s actually important? What does it mean for the person or for their family?
Judy - Yes, well I hope that’s where programmes like those that exist in the UK diffusely and elsewhere in the world, where people have tried to think about this ‘if’ issue. So, if you happen to have an alteration in a gene that’s well-studied like the colon genes or breast cancer, then there's information to help you know what that might mean for you and for your children, your siblings, your family members. If it’s a gene that hasn’t been so well-studied, then perhaps you're someone who can contribute your information so that we can have research now give information to the next group to come along.
Kat - And do a little future looking for me, where do you think we’re going to be, let’s say, in 5 years’ time in this kind of area?
Judy - Well, within 5 years, I think almost everyone will be having their tumour sequenced and that means that they will also have some of their own blood sequenced to try and understand the genetics, and for treatment that will be hopefully allowing us to use novel medications that are more effective and less toxic. And for our blood, it means we’re going to learn more about our risk of cancer and other conditions. And we’re going to have to think about how best to handle that information.
Kat - That was Judy Garber from the Dana-Farber Cancer Institute.