Research

People join AACR to get access to their journals and publications and to attend the (annual) meeting, but I see a big opportunity to build a much more interactive community, using social-networking types of technology as another way of communicating. So one of my main goals is to find ways of bringing people together more effectively to share information and to improve communications among the cancer research communities.

Well, the United States, compared to the rest of the world, is still the powerhouse of research on the basic biology of cancer. But funding is effectively shrinking, because our budgets are fixed but costs are going up. It's becoming increasingly difficult to get federal funding to support this kind of work.

I think it's a very dangerous and difficult time. We're losing a lot of people, because we just can't keep the funds coming in the door. It's difficult to keep people motivated to join the research community when they see how tough it is to make it in academia. Our lead position is being eroded, and if we lose a couple of generations of people we'll definitely lose a massive amount of momentum.

The good news is that quite a few genes that drive cancer have been identified and drugs have been developed that inhibit their actions pretty effectively, at least until drug resistance appears. The whole paradigm has changed; now we think of cancer as a large number of diseases, each characterized by different driver mutations so that each disease might respond differently to drugs.

The other big evolution of our thinking is that we now understand the complexity of the mutational spectrum of cancer cells. Deep sequencing of DNA from tumors has revealed a shocking degree of variation between individual tumors and a staggering number of mutations and other genetic changes within individual tumors — even within different tumors in the same patient. It is a sobering realization as we think about trying to treat cancers with targeted therapies.

If you step way back and look at the progress that's been made in the whole field, you would have to say that it has been incremental. We're just steadily chipping away, and people are living longer and responding better. But for some types of cancer outcomes for patients have improved dramatically.

The most obvious examples have been in melanoma. Two years ago there were no approved drugs that really had any significant impact on melanoma. Now there are drugs that hit subsets of melanoma, depending on which driver mutations cause the disease, and these have very dramatic effects.

And in lung cancer there also have been dramatic success stories — drugs that target the EGF receptor and the ALK protein for example. Although these target relatively small subsets in the spectrum of lung cancers, their effects are very dramatic, and they change the way we think about lung cancer. And in certain types of prostate cancer we also have made better-than-incremental progress.

Most of the progress to date really has been through identifying driver genes which cause subsets of cancer, and then drugs being developed that hit those targets. The number of new discoveries in that area is slowing down, and a very large number of tumors just don't seem to have tractable driver genes that we actually can attack.

Over the next five years, we'll see big improvements in therapy for the tumors we understand. In cases where there is a clear driver oncogene, we understand that we probably will need to use two or three drugs at once to get a really significant and sustained effect. That will be the nature of clinical research over the next five years — testing combinations of drugs that hit different parts of the cancer cells’ signaling networks to shut them down and kill the tumor.

But I think we're still waiting for another leap forward in technology, which will then enable us to attack the tumors for which we don't have any clear driver genes or any driver genes that we can actually attack with drugs. I'd like it to come along soon.

That is the challenge for many medical centers and community hospitals or wherever patients are being treated: How do you access the genomic technology so that we can really identify the mutational spectrum of the tumor we want to treat? That's a challenge for everybody in terms of cost, infrastructure and logistics.

Another major challenge is the testing of combinations of drugs and the development of biomarkers that tell us how each of the drugs is working and what the right dose is, and how to schedule the dose. In my role as the AACR president, I am leading a task force, working with the FDA to try and figure out how to do that most effectively.

The whole community realizes the issues that are involved and is working together quite effectively to try [to] solve the problem, but the big problems involve a lot of resources and a lot of regulatory issues as well.

It's true that many pharma companies are looking to academic centers to do their clinical testing of new agents because of the complexity of the issues that we just discussed — the challenges of identifying the right patients to put on a study, the challenges of developing different combinations of drugs simultaneously, and of developing biomarkers so we can actually tell how patients are responding.

Those challenges are often best met in academic centers like ours at UCSF, where we have the technology and the expertise and the infrastructure to do all the types of analysis that are necessary.

We are in ongoing discussions with most of the big, cancer-drug development organizations to develop partnerships to help them navigate and steward their compounds through clinical testing. I think academic centers will be playing an increasingly important role.

Industry is also looking to the academic world for guidance in terms of identifying new strategies for attacking cancer and for identifying targets. They themselves are pulling back from more basic research. There’s no abundance of resources in Big Pharma that can easily be applied to support basic research in academia, but in clinical drug development, the two are working more closely together than before.

Well, the single most satisfying thing so far is developing sorafenib [Nexavar]. It's a drug that's been approved to treat kidney cancer and metastic liver cancer.

Yes, it was my idea, and I started working on it, and in collaboration with Bayer Co. we developed it, and it became the first drug approved for liver cancer and one of the first for kidney cancer. That was a big moment for me. When the clinical data were presented for the first time at a meeting a few years ago, I had no idea what to expect, really. When it was revealed that our drug had a clear effect on patient survival, it was really gratifying.

One of the most appealing things about academia is the research environment, being surrounded by faculty, postdocs and students all working on different research projects from different angles. You can interact with really creative, smart people. There are a lot of seminars and intellectual exchanges in a really dynamic, intellectual environment.

In industry, you have the ability to push a project through. There are also extremely smart and competent people, but they are more focused on one goal. When we work in industry, it’s very clear that we're all going in the same direction, and that the goal is to get something to the clinic.

They're very different, but I've actually enjoyed them both equally.

Well, I still race a car when I get a chance. I drive a formula car, an open-wheel race car, and I very much enjoy weekends at the racetrack with my racing friends, just relaxing and thinking about different challenges. Getting out there on the racetrack is my major passion outside of work.

The opportunities for making an impact on cancer research have never been better. We know so much about the disease, and the tools are in place to really move things forward like never before. It’s the best time imaginable to be entering the cancer research environment from the point of view being able to make an impact.

But on the side of caution I would say that the research community is danger of shrinking in this country as the federal government pulls back spending on research, and it's a tough road to make it in academia, or in biotech for that matter. You have to be absolutely committed and dedicated to it to have a real chance of becoming an independent, successful investigator.

That said, a career in cancer research has the potential of being the most exciting and rewarding job you could possibly imagine.