SUSAN DENTZER: What I'd like to do now is just for the benefit of our viewers is do sort of a genetics 101 of cancer. What we now understand happened in-- in-- really any cancer in terms of the changes in the gene and leading down to the production of proteins, etcetera. So in the simplest possible terms, what do we understand now about the genetic basis of cancer?
LEE HARTWELL: Well what's-- unique about cancer is that-- it's-- it's a disease that involves changes in genes as it progresses. And so-- you know, most of the information that is available-- to the public talks about-- the inherited genes that can increase the risk for cancer.
And-- the ones that we know about account for only relatively small percentage of the risk of cancer. But-- but that just is about increased risk. Okay?
When a cancer actually starts in the body there are further genetic changes that occur progressively. And-- cancer cells have many, many genetic changes in them. We don't really know how many. But they're-- incurring those-- the damage to their DNA and their genes at an increased rate.
And that's the fundamental basis of the cancer process. Is changes in the genes during the course of the disease. And-- if it weren't for that, cancer wouldn't occur. Because-- single genetic change doesn't induce cancer. It takes a whole series. But-- as I say, those changes we can use them as diagnostic markers for the type of cancer and its presence and its response in various things.
SUSAN DENTZER: And as those gene changes take place, those are the gene changes that essentially prompt the cells to uncontrolled growth. Correct?
LEE HARTWELL: Yes.
SUSAN DENTZER: Could you say that?
LEE HARTWELL: Yeah, yeah, what the-- we-- we know about a whole lot of processes. And that's what I say about the knowledge that's accumulated about cancer. So-- cells normally-- are not dividing in an adult body.
And cancer cells divide more. So they-- getting signals or making their own signals to divide. That's part of the change. Normal cells, if they're in a situation where they shouldn't be dividing, commit suicide. And cancer cells overcome that process and they don't anymore. So that's another genetic change.
Normal cells will divide a certain number of times and then stop. There's a built in aging to normal cells. Cancer cells overcome that and become immortal. So these are all processes that have to mutate from a normal cell to produce a cancer cell. And we know of at least a half a dozen such processes.
SUSAN DENTZER: And does all of these-- genetic changes take place, the proteins that these genes are coding for are changing as well, correct?
LEE HARTWELL: Yes it can either be that-- the protein that does the functions, so the gene is the information to make the protein. The protein goes out, does the function. Some changes produce an excess of protein over the normal.
It's the same protein, but it's just a lot more of it. Other-- those are sort of growth promoting genes. Other genes get inactivated. So that a protein that's normally produced is not produced anymore. And those are the genes that normally put the brakes on cells and keep them from dividing. And so they get lost then the cells can divide more.
And-- then a third type of change is where the proteins produced is actually a different protein. And has some abnormal function.
SUSAN DENTZER: So when we think about looking for proteins as biomarkers, which of those various types of proteins produced in different ways or not produced are we-- are we looking for?
LEE HARTWELL: Well I think primarily what we're looking for is the presence of proteins-- in the blood or other body fluids that are not normally there. Or present in more-- greater concentration than are normally there.
So-- that's not necessarily a result of just the fact that the cancer produces a certain kind of protein. But cancer cells are very different than normal cells in that-- they're dying more even though they're dividing. They're dying more and releasing their contents.
They have a blood supply that's leaky. The blood vessels are leaky and proteins get out that don't normally get out. There are enzymes that chew proteins into funny pieces. And then there are the mutations that occur that make proteins different than normal. So all of those are possibilities for-- for biomarkers.
SUSAN DENTZER: It sounds like we're talking about a-- a practically infinite number of biomarkers.
LEE HARTWELL: Yeah the-- the-- the human genome-- encodes about 25,000 genes. And so each of our cells has the capability of producing these 25,000 different genes. Which you would think might each produce one protein.
But in fact there's ways of rearranging the information in the gene normally so that the typical gene actually produces several different varieties of that protein. And you know, probably ten to 100 different varieties.
And then there are modifications that occur to the protein to change it's activity later. So in fact it's-- it's-- there are-- there are tens to hundreds of different forms of each of the 25,000 different proteins. So there is a tremendous amount of-- different-- functional-- entities that are produced by cells-- that could provide diagnostic information.
SUSAN DENTZER: So does that-- all that add up to tens of thousands of potential biomarkers? Or even more?
LEE HARTWELL: Oh yeah I think tens of thousands at least. And-- and very possibly more. The problem is that the methods for discovering biomarkers have not been effective. And so we have a very small number of protein biomarkers that are actually used for diagnostic purposes.
We think that's gonna change dramatically over the next-- decade. Because-- first we have this catalogue of information from the human genome as to what could be produced. And that's-- that's important. We also have all this functional information about cancer and other diseases. So we know what proteins to look for as an informative.
And then thirdly, the instrumentation that's needed to look for these proteins has become much more sophisticated and functional in the last few years. So-- we're just beginning to be at the process where we can start-- finding these thousands of pieces of information. So at the present time it's a little hard to project-- how much information is there. But I think it's likely to be enormous.