New technology fueled by genomic research could soon make a simple blood test for cancer a part of ordinary visits to the doctor.

Question: What has your research revealedrn about the geneticrncauses of cancer?

Michael Wigler: Yeah. rnWell, the first observation was that there was a very strong rncorrelationrnbetween the extent to which the genome in a cancer cell has changed and rnthernlethality of the cancer.  So that,rnif one’s looking at cancer and there’s lots of changes in the genome, rnthatrnpatient is less likely to survive than a patient whose genome has just rnbegun tornevolve.  That was the first majorrnobservation. 

There were a lot of particular details that emergedrn fromrnthose studies, that is, we found the locations of genes that are called rnuncArngenes and tumor suppressor genes. rnThe individual genes at these places, many of the changes are rnwhat werncall recurrent.  They happen overrnand over again in different people with the same cancer, and there are rngenes inrnthose regions that one can show functionally alter the capacity of the rncancerrncell to grow, divide, or spread in the individual.  Sorn this has been an engine also for the discovery of newrncancer genes. 

We weren’t the first ones to do this. rn People have been using these techniquesrnfor a while, including ourselves, for a period of 10 years or more.  Sometimes particular drugs that arerngiven to a patient are determined by whether that patient has a rnparticular genernamplification in their cancer.  Thernmost well-known example of that is patients with amplification of the rnHER2rngene will likely respond to Herceptin. rnSo, our review has been that specific amplifications will rncorrelate withrndrug sensitivity, we’re in the middle of exploring that, and we’ve also rnbegunrnto look at single cells within cancer. rnSo that we can now actually look at the genome of an individual rncellrnwithin the cancer and that’s giving us a much more detailed picture of rnhow therncancer has evolved. 

So, we think we’ll be able to identify, for rnexample, the earliestrncells, the earliest mutations in a cancer that will tell us how the rncancerrnbegan to grow in the first place. rnIt will also tell us what you might call the tribal, or rnpopulationrnstructure of the cancer, and that tells us about how the cancer is... rnhow thernindividual cancer cells are interacting with each other, interacting rnwith thernhost, and migrating through the cancer, and possibly migrating rnthroughout thernpatient.  So that we think that byrnlooking at the individual cells of the cancer, we’ll be able to improvernclinical staging and drug treatment enormously.  Butrn this is a long-term project.  This will take us rnfive years, 10 years.

Question: How might this research impact rnclinical cancerrntreatments?

Michael Wigler: Well, I can give you two rnways—there are manyrnways this research could impact the clinic.  I canrn give you two very concrete examples.  If a new rndrug is being tested in arnpopulation with a particular type of cancer, one might look for rncorrelationsrnbetween response to the drug and the genome profile.  Thatrn could tell you which patients are likely to respond torna drug so that patients don’t have to take a drug that’s not going to rnbenefitrnthem and don’t have to suffer the side effects of a drug that’s not rngoing tornbenefit them.  And that willrnultimately lead to the design of better drugs.  

A second way—and this next way is not quite sciencernfiction, but we’re looking a little bit into the future—when we can rnexaminernthe genome of individual cells, and can do that cheaply, we can develop rnearlyrndetection tests for cancer that are based on blood.  So,rn it’s now being appreciated widely that even cancers thatrnperhaps have not yet metastasized release their cells into the rnbloodstream andrndo so in fairly large numbers so that you can collect cells from the rnblood andrnidentify them as a kind of cell that shouldn’t be in the blood.  But people haven’t yet been able tornlook at the genomes of these individual cells.  So,rn some of the methodology that we are developing willrnenable us to do that.  So you canrnimagine that at some time in the future, you can draw blood in the rndoctor’srnoffice and just like the doctors now do what’s called a blood count torndetermine how many white blood cells you have, whether it’s likely that rnyou’verngot a fever, they’ll be able to sort out from the blood this small rnproportionrnof cells that might be being spun off by a cancer somewhere undetected rnin thernbody.  And by looking at the genomernof those cells, and possibly by also looking at the RNA that those cellsrn arernmaking, I'll be able to say "This person has malignant bone cancer," andrn then yourncan look for that. 

So, this technology can ultimately lead to early rndetectionrnfor cancer.

Recorded April 12, 2010