PORTLAND, Ore. — For the health care and research fields, cancer has long been a most implacable and deadly foe. But there are advances in the fight against it happening more and more — some of them happening here in Portland, inspired in part by the brilliance of one local doctor.
Brian Druker is a medical doctor who grew up in Minnesota. He went to medical school in California and began his research career there.
In 1993, OHSU recruited Dr. Druker to come to Portland and open a lab focused on targeted therapies for cancers. It was there that he found a compound that would zero in on a genetic mutation in the cells that caused a specific type of leukemia called "CML."
The problem was that the leukemia cells kept dividing because a molecular switch was stuck in the "on" position. Druker's compound would target those cells and shut off the switch, while at the same time leaving healthy cells alone. It became a drug called Gleevec — or imatinib, if you get the generic variety.
The drug has saved thousands of lives since it was approved back in 2001 by the U.S. Food and Drug Administration. Someone with CML who takes Gleevec and is in remission two years after starting treatment will live a normal lifespan.
The Story's Pat Dooris recently sat down with Druker to talk about the drug and the new era of precision medicine that his discovery launched.
A wealth of memories
Brian Druker: Well, precision medicine is where we started, and that was my own background. In the drug I developed called Gleevec ... leukemia had a three- to five-year life expectancy, and now, patients are expected to live a normal lifespan.
Pat Dooris: Which is amazing ... And by the way, I had a question — one that I think people at home wonder: You developed this thing that saved bajillions of lives. Did you get wealthy doing that?
BD: You know, the drug, when it came into my lab, came from a drug company, and it had this unusual patent against any tumor in a warm-blooded mammal. Unless we determine that it could treat snake cancer, we saw zero profit from it, and I get no royalty, so ... No, I didn't get wealthy from that. But the wealth that I have is that at least once a week I get an email in my inbox from a patient who has benefited from this medication, and what a remarkable reward to get an email at the end of a long week that said, 'Thank you for this drug, and here's all the incredible things I've done over the last decade.'
And just last week, I was visited by a gentleman from England, 10 years on therapy. He brought me pictures of him skydiving, climbing Mount Kilimanjaro, and he just wanted to come and thank me. And I can't think of anything more rewarding than that.
PD: So, wealth of memories. OK, but I took you off track.
BD: But what we want is we want that outcome for all patients with cancer by trying to match their unique and individual cancer with better treatments and better outcomes. So what we've learned is that we need to analyze tumors in incredible breadth and depth.
PD: And before you go into that, as you're saying that I'm thinking in the old days, like chemotherapy, that was basically carpet bombing the body, right?
BD: Yeah, that's exactly the analogy I'd use. It is carpet bombing. It's slash and burn, and it leaves our patients pretty bruised and battered.
PD: And so now, you're able to target ...
BD: Let's look at what distinguishes your cancer cells from normal cells and use that to design a treatment that matches your cancer. But what we've learned over the last five to 10 years is cancer is a pretty tough enemy, and we throw something at it and it figures out a way to circumvent it and become resistant.
So we've designed a program called SMMART — with two M's because we can't spell. But we're trying to outsmart the cancer by taking a biopsy on treatment and trying to figure out how is it trying to evade and evolve on treatment. So now we can come back and revamp our treatment, just try to stay one step ahead of it. And by doing those sorts of testing in analytics, we can take people that might have only six months to live, and oftentimes, they'll be getting years. So we're adding years to people's life, but now, we want to move that up earlier, where we think we could actually think about curing more people with less harm.
Staying on target
Druker is still at OHSU, now as the CEO of the Knight Cancer Institute. With Gleevec, he found a way to give thousands of people a new lease on life. He joked with Dooris that he now tells leukemia patients something like, "Sure, you will die someday, but not from this."
One of his areas of focus, as he mentioned, is precision: how to kill cancer cells with very targeted attacks. Another focus is on finding cancer earlier, when it is very small and just taking root.
BD: A decade ago, and I said we need a blood test for cancer at early stages. It sounds a little bit like science fiction, and it kind of is when you look, when you follow the science — it's incredible science. But the reality is it's now available to help people and detect cancer at these earliest and curable stages.
PD: Are you able to dumb it down enough to explain to a guy like me how a simple blood test can find particular cancer?
BD: The way that I explain it, Pat, is if you look at any cell in your body, the DNA in each cell is 100% identical. But you have a lung cell, a liver cell, a heart cell. So how does that DNA know how to make a heart cell or a lung cell or a kidney cell? And what happens is there's almost like a marking pencil that goes along the DNA and says, 'We're going to activate the heart program and deactivate every other program.' And when you shed some cells into the bloodstream, we can detect, 'Hey, you had a couple extra drinks last night and we can see you shed a few extra liver cells into your bloodstream because you killed a couple liver cells.' So we can detect those marks in the bloodstream.
Similarly, cancer, because it has to grow, divide, survive, spread around the body, it gets very specific marks in the DNA that identify it as a cancer. So now when we take a blood sample, we can tune an algorithm to: is there cancer? Yes or no? Meaning, do those marks show up? And if the answer's yes, we can then go back and say, 'Does that look like it's coming from a liver cell, a kidney cell or a lung cell?' Now, we can go back, and it looks like it's a lung cell. We may do a chest X-ray and see what's there. So it's just an amazing biology of how our bodies grow and develop. And we're just taking advantage of that.
Thinking big
These days, Druker is not just a scientist and a doctor who sees patients — he's someone who thinks big. He inspired and is now running the Knight Cancer Institute, which is a pretty big deal. Nine years ago, he helped raise a billion dollars for the institute, starting with a $500 million matching pledge from Nike founder Phil Knight.
Pledges included $100 million from the late Gert Boyle of Columbia Sportswear and $200 million from taxpayers through the Oregon Legislature. The rest came from a number of companies, including The Standard and Hoffman Construction, and a variety of smaller donations.
Suddenly, Druker had a billion dollars at his disposal and mandate to build out the Knight Cancer Institute to make it a preeminent research center for the West Coast. Druker helped design the building to house the research center, and he began recruiting the best talent in the world.
BD: We're now up to 1,500 people that we've brought in, so we've surpassed the goal of 1,000. And again, it's just something I'm really proud of is that we've built a great team here of people that want to make Oregon the place where we end cancer as we know it — and that was what the purpose of the challenge, the point of the challenge was. And we're living up to it.
PD: It's obvious to you, but what are some of the benefits of having 1,500 people all together in one campus or one building?
BD: Yeah, it truly brings a critical mass of people. I'll tell you a little bit about our early cancer detection program ... we've deliberately designed it to be multidisciplinary. So it's cancer biologists, it's mathematicians, it's engineers, it's computationalists, it's all sorts of different disciplines to try to attack a huge problem to advance the field. And I've always talked about this kind of like a Bell Labs. It's bringing lots of different disciplines together, bringing them and focusing them on a problem and then watching incredible things happen.
PD: And it sounds pretty easy when you lay it out like that, but I imagine there must be a tremendous amount of pressure for you, as sort of the founding force behind all this.
BD: Of course, there's pressure and responsibility. But by hiring great people and letting them create, they do incredible work. Just to give you an example, a decade ago when we started the challenge, we talked about what we really need is a simple blood test for cancer. And working with a company in the Bay Area, we've launched blood testing to identify 50 different cancers at early stages — and just to give an example of the impact that's had, there was a retired family physician who enrolled in one of our studies. We found an early stage bile duct cancer. That typically isn't detected until very late, untreatable incurable stages. We identified it at an early enough stage, (it was) able to undergo a curative surgery. Those are the sorts of things that are happening here and that we're bringing forward to our communities into the world.
PD: I had read about ... You told (KGW's Laural Porter) a little bit that you were in 2021 just starting to work with that company. And as I was listening to that, I was worried it was Theranos.
BD: Yes. Theranos, you know, we hear about Theranos all the time. But to give you an example, this is real-world data. This is already being tested in 140,000 people in a randomized trial in England to try to establish this as a new benchmark for early cancer detection. The National Cancer Institute in the U.S. has invested in these types of technologies that are real and have real patient benefit. So yes, I understand there's some tarnish from Theranos, but this has real data benefiting real people.
We're also working on the next generation of blood tests. We're looking at other markers that could get shed into the bloodstream, not just DNA, but also proteins that get released by cells and also tiny little packages of protein or DNA get released by cells every single day and we're trying to understand how cells communicate with one another. So we're looking at all these signals that our bodies are trying to say, 'Hey, there might be a cancer somewhere or a signal that something just isn't quite right with the immune system that's trying to identify a cancer.' All these things are happening. And we're trying to track down these signals.
PD: So, does this mean that one day doctors will be able to figure out what cancer we are most likely to get and help us defend against it?
BD: I think through blood tests, yes, there can be — and I think in the next generation of the sorts of projects that we'll look at, it will be how do cancers evolve over time. And if you think about smoking and the damage it does to the lung, can we detect some of the damage that's going to lead to a cancer, and then maybe could we reverse that? Of course, not smoking would be way better. But we also know that people, even after they stop smoking, will have a slightly higher (risk) 10-20 years later, still have a higher risk of cancer. Are the things that we could do that might prevent that? But also, I'm afraid as you and I get a little bit older, there are also other things that we can identify and blood tests that tell us our risk of cancer is going up as we age. Could we think about intervening to reverse that and reset the clock? Maybe then we wouldn't even get cancer in the first place. That's the next generation of projects we'll do.