UCSF's Frank McCormick Now Leads World's Largest Cancer Research Association

UCSF cancer researcher and race car driver, Frank McCormick discusses his views on progress to date in the battle against cancer, and shares his vision for what’s ahead, including his new role as president of the American Association of Cancer Research.

Frank McCormick, PhD, FRS, director of the Helen Diller Family Comprehensive Cancer Center at UCSF, was elected president of the 35,000-member American Association of Cancer Research (AACR), the world's largest organization of its kind dedicated to prevent and cure cancer through research, education, communication and collaboration.

His term began at the group’s annual meeting, which is taking place — fittingly enough — at Chicago’s McCormick Place and runs through April 4. It’s the world’s biggest meeting for cancer researchers.

McCormick was vice president of research for Cetus Corporation in the 1980s — still the early days of biotech — and in 1992 he founded Onyx Pharmaceuticals, where his pioneering research led to the development of a treatment for kidney and liver cancer. In 1996, McCormick was made a fellow of the Royal Society. He joined the faculty at UCSF in 1997.

In this interview, McCormick discusses his views on progress to date in the battle against cancer, and shares his vision for what’s ahead.

Q: Do you have a particular agenda that you would like to advance as the new president of the AACR? What is it that most appeals to you about this opportunity to lead the organization?

A: People join AACR to get access to their journals and publications and to attend the 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. I also see an opportunity to expand the influence of the AACR overseas. There has been a tremendous growth in research in China and India and other countries, and the AACR needs to be out there and represented in all these different research communities.

Q: How healthy is basic research on the biology of cancer in the United States?

A: 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.

Q: How has scientific thinking about the problem of cancer been changing in recent years?

A: 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. So, for example, we don’t think about lung cancer in a general sense, but instead, in terms of lung cancers caused by EGF-receptor mutations or by ALK mutations or by K-ras mutations. We think of these as separate entities, and treat them differently.

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.

Q: Would you characterize the progress being made to prevent and cure cancer as incremental? If the time has not already arrived, do you foresee a time on the horizon when advances in research and drug development result in treatments that dramatically improve outcomes, as we have seen with HIV and now are beginning to see with hepatitis C?

UCSF’s Top Discoveries in War on Cancer

  • Discovered the existence of cancer-causing oncogenes, which led in 1989 to a Nobel Prize in Physiology or Medicine for J. Michael Bishop, MD, and Harold Varmus, MD. The discovery opened new doors for exploring genetic mistakes that cause cancer. The landmark work formed the basis for some of the most important cancer research happening today.
  • Discovered the molecular nature of telomeres – parts of chromosomes that critically affect the life span of cells — and the enzyme telomerase that regulates them. Telomeres and telomerase play a key role in cell aging and in cancer, and telomerase is now a therapeutic target for cancer and other diseases. Groundbreaking work on telomeres and telomerase led to a 2009 Nobel Prize in Physiology or Medicine for UCSF scientist Elizabeth Blackburn, PhD.
  • Pioneered an adaptive clinical trial design to accelerate the translation of research into breast cancer care. The new type of study, which involves repeated magnetic resonance imaging and tissue analyses to direct changes throughout the course of the trial, aims to quickly gauge the effectiveness for each individual patient of experimental therapies as additions to standard chemotherapy.
  • Pioneered and proved the effectiveness of a mapping technique that allows for the safe removal of tumors near language pathways in the brain. The technique minimizes brain exposure and reduces the amount of time a patient must be awake during surgery.
  • Spearheaded the development of immunotherapy for prostate cancer, which uses a patient's own immune cells to help fight the disease. UCSF led the clinical testing of a vaccine that improves survival and that was the first immunotherapy to gain Food and Drug Administration approval.
  • Developed a new diagnostic test using genetic markers that can help distinguish benign moles from malignant melanoma. The test is the first to demonstrate both the diagnostic accuracy and the practicality of a multi-biomarker approach to diagnosing melanoma. Read more

A: 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.

Q: How do you envision progress going forward?

A: Well, 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.

Q: How well organized is the clinical research enterprise in the United States to evaluate and commercialize the most promising treatments? Are combination therapies and treatments that are likely to be effective — but only for subsets of patients — being investigated in a way that matches their promise? Does the nation’s research infrastructure need to change in any way to better realize the promise of new scientific discoveries and drug developments?

A: 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 and solve the problem, but the big problems involve a lot of resources and a lot of regulatory issues as well.

Q: How do you see the role of university-industry partnerships evolving in cancer research? Will there be more collaborations? Is it likely that university researchers will be expected by industry partners to expand into drug development and pre-clinical testing of lead compounds to engage interest from pharma or biotech, or will much of that risk-taking continue to be shouldered by the commercial sector?

A: 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.

Q: What career accomplishment has given you the greatest satisfaction?

A: 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.

Q: That was based on your research?

A: Yes, it was my idea, and I started working on it, and in collaboration with Bayer Company 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.

Q: Having done both, what do you think is most appealing about working in academia and in industry?

A: 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.

Q: What do you like to do these days when you're not fighting cancer?

A: 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.

Q: What advice would you give to talented undergraduates who are thinking about training for a career in cancer research and getting ready to apply for graduate school or medical school?

A: 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 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.

Photo by Noah Berger

Margaret Tempero, MD, UCSF professor of medicine and deputy director of the Helen Diller Family Comprehensive Cancer Center, explores new strategies for prevention, diagnosis and management of cancer for UCSF's Mini Medical School for the Public on UCTV.