39-42 – Conversation with The Cancer Letter

Conversation with The Cancer Letter

Wicha to Leave Director’s Job at UMich

After 27 years and six NCI cancer center support grants, Max Wicha announced he would step down as director of the University of Michigan Comprehensive Cancer Center.

“Frankly, my research is really going well now,” Wicha said in a Q&A with The Cancer Letter. “It’s in a very exciting phase in researching cancer stem cells. My lab has grown—and my work is now moving into the clinic, so I’m actually working with our clinical people to do clinical trials targeting cancer stem cells.

“So the idea of five more years, or do I get to really focus on my research now? That was really the deciding factor.

“So it’s time. Again, six core grants is quite a number.”

Wicha’s announcement is part of an unusual exeunt of the three longest-serving directors of NCI-designated comprehensive cancer centers.

His friend Steven Rosen announced last week that after 25 years as director of Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, he would leave to become the center director, provost, and chief scientific officer at City of Hope National Medical Center (The Cancer Letter, Nov. 1).

“It’s not a cohort effect,” quipped the third longest-serving cancer center director, Shelton Earp, who is finishing his final weeks as director of the University of North Carolina Lineberger Cancer Center. Earp, who became the center director 16 years ago, will remain in his job as director of UNC Cancer Care, where he will be planning clinical operations. “I am not going anywhere. I’ve been here since 1966, so I am part of the woodwork.”

It’s not immediately clear who would be the longest-serving cancer center director would be after the Wicha, Rosen and Earp trio leave their posts.

Wicha spoke with Paul Goldberg, editor and publisher of The Cancer Letter.

Paul Goldberg: You are the dean of the cancer center directors. It’s kind of difficult to process that you will be leaving the director’s job.

Max Wicha: It’s certainly been a long time: 27 years.

PG: I remember sitting in your office and realizing that a year ago. It was kind of like, has it been 26 years?

MW: It is hard to believe.

PG: Why would you be leaving now?

MW: I think that the way cancer centers work is on five-year cycles.

I’ve done six core grants now; I think that might be the record. I don’t know whether anyone’s gotten six core grants. So I had to really decide whether I wanted to do a seventh, which would take me another five years.

Frankly, my research is really going well now. It’s in a very exciting phase in researching cancer stem cells. My lab has grown—and my work is now moving into the clinic, so I’m actually working with our clinical people to do clinical trials targeting cancer stem cells.

So, the idea of five more years, or do I get to really focus on my research now? That was really the deciding factor.

So it’s time. Again, six core grants is quite a number.

PG: It is pretty astonishing. Reflecting on your long, distinguished career now, what would be the high points and what would be the disappointments?

MW: Well I think that, rather than a high point, what is really exciting is what has happened over these past 27 years in the science. It’s so exciting to see the advances.

When I was starting in the late 1980’s, we really had very little concept about what the cancer was really being driven by and how we could attack it better scientifically.

Cancer was really all empirical science—all trial and error.

What we’ve seen over the past 27 years is this great advancement in science, and that’s the really exciting part.

I think I can even have more of an impact now in my research. The challenge is the application of basic concepts in the biology to the treatment, and there it really lags behind.

We really haven’t seen the fruits of this new research pay off, and see patients doing that much better yet—although I’m really very much of an optimist, because I really do believe that we’re on the cusp of some great advances that are going to improve the outcome for patients.

So that’s kind of the frustration; that that part didn’t happen quicker. But it’s happening now, and it’s a very exciting time. So, to be part of that, and kind of in the leadership of that, has been a great satisfaction.

When I got into this 27 years ago, I loved the research then, too, and I had a clinical practice, too—but the decision at that time was whether I would have a greater impact if I I would take a leadership role. I could help shape the programs themselves, rather than just doing the research myself.

That was the major decision I made, but I kind of got into it at a much earlier age than I ever would have planned.

When I became the cancer center director I was only 37 years old; I wasn’t that far out of my training.

One thing I thought was pretty amusing: when I did my first site visit and I was so young, the site visit team looked at me and said, “Aren’t you awfully young and inexperienced to try and build a new cancer center?”

And now on my last site visit, being the sixth one, they are saying: “Aren’t you getting a little old here? What are your plans for succession?”

So I figured I had come full circle because here I was getting the two questions on the bookends of my career.

It’s just been a wonderful experience to be a cancer center director.

PG: It must have been. Given this long tenure, what do you think of the NCI cancer centers program as you’ve seen it evolve? Is it still the jewel of NCI?

MW: Absolutely.

I really believe strongly that it is, because almost all of the big breakthroughs in cancer research have come out of the cancer centers. It’s been the jewel in the world, I think, because we’ve really led the world in cancer research.

One of the strengths of the centers is that they can leverage a lot of resources.The core grants are critical, they provide the infrastructure and nucleus, but all of us can leverage this with philanthropy and other resources and bring together teams.

Because what I’ve seen over the past 27 years has been growth of team science. Twenty-seven years ago, there wasn’t much team science.

Everybody was doing their own thing, and there was good R01 science. The R01 science provided a lot of the good underpinnings of things, but it was hard to get things to move into the clinic.

You had to put teams together to do larger-scale research, and that’s where the cancer centers have really thrived, in putting teams together to focus things.

PG: So team science is it—that’s really the change?

MW: The team science has been a huge change over this time.

Another thing about the cancer centers that I think has been very gratifying has been that the community of cancer center directors is a very collegial and close-knit team.

I don’t know, over the years—I know you’ve been covering it so long—whether you’ve appreciated this, but in academic medicine in general there’s a lot of competition, because people get rewarded when they achieve something, so they want to compete against other people.

But cancer center directors have remarkably always worked together and helped each other out. We serve on each other’s scientific advisory boards—right now I’m on seven boards, and I’ve served on over a dozen advisory boards. We really give each other our best advice, so there’s much more of this feeling of collegiality rather than competition.

And again, that’s been really great.

Throughout the whole time, it’s been a really good group of people—because, also, the kind of personalities that do well as cancer center directors are people who are good at interacting with other people and getting groups to work together.

So I think that that helps them interact well with each other, too.

PG: You might have had something to do with that spirit of collegiality.

MW: I’ve tried to foster that over the years.

If you just look at the people who are cancer center directors, their personalities, they’re really friendly people.

They are not the aggressive, cutthroat people—they are really team-building people. That’s why they get along well. As a matter of fact, if someone gets a job as a cancer center director and they are not really collegial, they don’t do very well, and they don’t last very long.

PG: Well, looking at the story about City of Hope last week, I realized how much is expected of a center director.

MW: I think the director really sets the tone for a cancer center, and in part, usually, the cancer center selects a director that fits what they need in their skill set, but in part it’s the other way around.

Directors kind of shape the direction of their centers. I think that was recognized early by the NCI, because whenever a new director comes in they give them some time, a few years to try and shape the center, and take it in the direction that they want to go.

That’s why I thought, in my own timing of this, that I wanted to let our dean do a national search.

A new director would come in and have two to three years to put the next core grant in, so they would really have time to look and shape it and take it in the directions they want it to go.

PG: I’m just thinking of the job descriptions. For example, you have to be a scientist, a science administrator, head of a huge health agency, a fundraiser—can anybody really do all that?

MW: That’s what makes it so much fun.

There are so many different parts to the job that it keeps it really challenging.

It may sound corny, but it’s true: you never know exactly what to expect. You’re dealing with so many different people and different groups—I’m sure that there is some overlapping, but there are different challenges between the matrix cancer centers and the free-standing cancer centers.

In the matrix cancer centers, the cancer center directors—because they don’t have a direct line of authority—essentially their authority comes from examples, and by providing a positive impetus for people to work together.

There is kind of no stick, it’s all really carrots.

As a matrix cancer center director, you learn to work with very diverse groups of people, including department chairs, who sometimes feel that there might be competition for resources—and you have to work with the chairs to really demonstrate that it’s a mutual gain when you do this well.

The directors over the years that have done well have worked very well within those structures. Ones that try to fight the structures, and think that they want to have more hierarchical models, they don’t do well in university-based centers.

PG: I’m thinking about how NCI support is not increasing; it’s actually decreasing. How would you regard the fact that there are emerging cancer centers and there are quite a few that are going through the process now—what is the value of the designation?

MW: The designation has tremendous value, because of its leveraging effect. I think that the frustrating part is, because the budgets are so flat, that it’s very hard to reward centers for doing very well.

So, essentially, in a very flat budget, if you do very well, you get to keep the budget. If you don’t do well, they will cut your budget.

There’s no real chance of increasing your budget.

But I think that, given those constraints, the reality of the situation is that cancer center directors now have to look to diversify the portfolio of how they support their cancer center program grants.

And I think we’ve all realized that, particularly over the past four or five years. For instance, working with industry has become much more important than it has in the past, for several reasons.

One is because the NCI support is flat. Basically you may get a little bit more of the pie, but the pie isn’t going to get any bigger.

And there are a lot of opportunities within the industry and with biotech. Because of the translational nature of research, working with industries and biotech is the only way to go anyway—because if you want to get your ideas into the clinic, you have to work with companies who have the expertise in how to do that.

I’ve had a lot more experience myself over the last five, or even 10 years now in trying to do that. I’ve started a company myself, along with Michael Clarke, OncoMed [Pharmaceuticals Inc.], which went public this year. It had its IPO, and the company now has five drugs in the clinic. It’s very gratifying actually to see that.

Our cancer center has now spun off 10 companies, and this was unheard of 10 years ago. You’d never think of cancer centers spinning off companies.

But that’s the new models we have to look at to be more entrepreneurial, because of the flat budgets at NCI.

Frankly, I’m more concerned with NCI’s support of other researchers, particularly young researchers, because I think that cancer centers do have much more flexibility in terms of these other diversified sources, including philanthropy.

But young researchers are getting very discouraged by the difficulty of getting grants from the NCI, and it’s discouraging some of them from going into research—that’s what I’m most concerned about.

PG: Do you think the industry understands the value of team science of the sort we were talking about a few minutes ago?

MW: I think they do, because industry has always had to do team science. The only difference is that most industry has had very hierarchical team science, where the head of the company dictates what the team does.

Now, there are some companies that have been much more entrepreneurial, like Genentech, that have allowed more ground-up research. But I think that they’ve always had teams that work together.

Now, I think what companies are seeing is that by working with cancer centers and academic institutions, it’s actually a partnership with many mutual gains—because they don’t have to invest as much in the early parts of research, because they’re being done well in cancer centers.

It can really be a win-win situation when they invest in the back-end of the research, the translational part, moving it into the clinic.

But they do that in teams too. In our cancer center, we have some new kinds of relationships with companies—for instance one with MedImmune, which is owned by AstraZeneca now.

They actually fund basic research in our laboratories that use compounds they’re developing, with the idea that basic research can then move into clinical trials with those same compounds, and they can then take advantage of the basic research that they funded. And I think that’s one of the new models that cancer centers will be doing more and more of in the future.

PG: Will the next of your focus be on targeting cancer stem cells? Will it be the lab? Will it be entrepreneurial?

MW: My research is in targeting cancer stem cells. My lab group—I’ve got about 30 people in my lab now, it’s actually grown—is not only studying the pathways that regulate cancer stem cells, but that’s the basic research.

We’re also working with a series of companies, at least six or seven different companies now, to take drugs and move them into clinical trials.

Our cancer center has 10 clinical trials going on now targeting cancer stem cells, and we’re working on new technologies to follow patients on these trials, things like circulating tumor cell assays. And that’s very exciting now too.

Some of these new technologies involve collaborations with very different kind of scientist. About two years ago, I moved my own laboratory, even though I directed the cancer center.

The university purchased a very large campus that’s right on the periphery of the campus—it’s about a mile and a half from the cancer center, and there are 150 acres and about 2 million square feet of space.

We are using this to develop a translational campus.

First of all, we’re bringing together people from multiple schools from across the university to work on common problems. So I share lab space, and the 30 people that are in my lab, with engineers from the school of engineering to work on microfluidic systems to capture these cancer stem cells.

We work with researchers from the College of Pharmacy to develop new compounds. We have a big drug discovery unit there too.

So, to me, that’s why moving into this next phase of my career is really exciting, because I’m in the middle of this new collaboration with other kinds of scientists as well as with industry—and I’m hoping that we’re going to see, over the next five or six years or so, some very exciting results coming out of the clinic in targeting cancer stem cells.

PG: And you will be able to stay, that wouldn’t be a problem?

MW: That was the plan all along.

I still have a clinical practice too, so I’ll be maintaining that—but I’ll have considerably more time to devote to this research, which is in a particularly exciting phase, so I think it works out really well for everyone.

PG: Do you think that in the future, the near future, or even now, that everyone will have their genome sequenced? Do you see any usefulness to banking this kind of information, just in case something pops up?

MW: I think that we will be moved toward doing a molecular analysis.

In our cancer center, under Arul Chinnaiyan’s [professor of pathology and urology at the University of Michigan, and Howard Hughes Medical Institute investigator] group we now have a program where we can do a deep sequencing of every patient who wants to go into an early-phase clinical study.

So we’ve done about 250 patients now, doing a deep molecular analysis, including both analysis of their tumor as well as germ-line analysis. We have set up a program called MI-ONCOSEQ so that Dr. Chinnaiyan and his group can do the whole analysis within a three-week period.

We have a molecular tumor board to see if they’re actionable and that they are patients that we can target.

But I think that’s only part of the answer—because that’s part of the genetic heterogeneity and the genetic analysis of tumors. In addition, the cancer stem cells suggest a whole other level of complexity, in which we have an epigenetic regulation of cells.

So what we really need to know is not only the mutations of each cell, but its expression pattern. And that’s what I’m working on in the lab with the engineers, to develop ways of single-cell analysis.

So from circulating cells in patients’ blood, we can do both a mutation analysis, as you’ve described, but also expression—so we can see which cells circulating are stem cells, and hopefully that will allow us to monitor patients on clinical trials, with these new stem cell therapies, to see if we can knock down the cancer stem cell populations.

Ultimately, we have to prove that it benefits patients—that they live longer.

PG: What’s your biggest concern now about where things are going in cancer research?

MW: My biggest concern is the young generation, again because of the funding situation.

I’m really concerned that we are going to lose the best and the brightest minds in the young generation that we’re going to desperately need to push this molecular therapy into the future.

The training that’s required to do this sophisticated translational research is really quite intensive. Some of my generation of oncologists, frankly, wasn’t trained in the molecular analysis to be able to move on to do that.

Most of the younger oncologists now know that it’s the future that they need to get into. But they get discouraged because of the difficulty of being able to get funding and having an academic career.

I think they are also concerned that potential decreases in reimbursement in the field in the future will make it harder to free up more time for them to do the research—they’ll have tremendous responsibilities in the patient care arena.

That’s my biggest concern, preserving the best minds to go into cancer research in the future.

PG: What would be your advice to the person who would replace you in this job?

MW: I think, to start out, it is to really listen.

We’ve got some really good leadership teams and I’ve got some really good associates.

That’s what made my job easier and much more doable, and because of that I’ve been able to do significant research while running the cancer center. It would be hard without the senior leaders. I would think that a new leader would take a lot of advice from the expertise we already have in place.

Once that’s done, they have the chance to take their own vision and superimpose it on what we’ve done already and figure out where it’s going to go in the next 25 years.

I’m not sure if my replacement is going to last 27 years, but whether they do or not, the important question is: how do you take what we have now, and move it forward.

I tell the young people now who are getting into research that I’m convinced that, during their time of research, that a lot of the things we’ve done in the past will become completely outmoded.

Some of our treatments, like chemotherapy, I hope, will be totally replaced by much more sophisticated, targeted drugs—and that they really need to go into this field to see some dramatic improvements in cancer. It will be particularly gratifying to see these changes, because they have been awfully slow.

I mean, I would have hoped, 27 years ago, that by now patients with common solid malignancies would have a better outlook, and we haven’t seen it yet. I’m optimistic that we will be seeing it soon.

PG: Is there any chance that you will change your mind?

MW: No. I’m very comfortable with my decision. I’ve taken this cancer center I think about as far as I can now.

It’s a wonderful place, and we have wonderful people, but it’s time to let someone else see what they can do.

In the meantime, I think that I have the opportunity to do some really exciting things in the research arena.

That would be the perfect complement to what I’ve been able to do as a leader in building a program—being able to really see some of my own research pay off, and improve some patient outcomes.