Rosenthal, Eric T.
Despite some seemingly obvious differences, the cancer research enterprise and entertainment industry share some substantive sociological similarities.
They both have strong star systems with A lists and B lists, along with some prima donna players with not exactly small egos who are used to dominating their own respective marquees.
So imagine a producer wanting to make a major motion picture and auditioning only A-listers who are told they must take co-starring or even supporting roles if they want to be considered.
Such was the somewhat analogous case when some of the eight finalist teams for the five available spots were informed they'd be switched around, traded, or consolidated to complete the dream teams that the Scientific Advisory Committee had envisioned could produce the best science to fulfill the mandate set forth by the Stand Up to Cancer (SU2C) Hollywood-based organizers—to have some impact on cancer patients within the three-year, average of $5 million per-year per-team grant period.
When I first interviewed committee chair Phillip A. Sharp, PhD, in OT's 9/25/08 issue, about how he and his vice chairs, Arnold J. Levine, PhD, and Brian Druker, MD, would evaluate the 237 grant submissions, Dr. Sharp said that in addition to the standard criteria, it would be the committee's prerogative to reshape the concepts or teams to determine the best configurations that might lead to the most creative results.
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He also said there was a possibility that the committee could put together a team de novo without anyone else suggesting it.
This “grand experiment” approach sounded good in theory, but when proposed and actually implemented, the result included some pushback, especially since some of the finalists were quite content with their proposals as submitted and didn't want to be second-guessed or told to rethink their approaches and work with what might have been construed as competitors in a less collaborative environment, according to some sources.
But part of this new paradigm in translational research included reviewers who were not the usual governmental bureaucrats, but were rather what was being called a “blue-ribbon” committee led by Nobel Laureate Sharp, Institute Professor at MIT and its David H. Koch Institute for Integrative Cancer Research; Dr. Levine, professor at both Cancer Institute of New Jersey, Robert Wood Johnson School of Medicine, and at the Institute for Advanced Study at Princeton, and former president of Rockefeller University; and Dr. Druker, Director of Oregon Health and Science University's Cancer Institute, who is perhaps best known for his role in developing imatinib.
Stronger Proposals Greater than Sum of Original Ideas
The three and their colleagues on the committee foresaw that better integration of basic and clinical teams filled with their respective superstars could create what Dr. Levine said during a phone interview were stronger proposals greater than the sum of the original ideas. He also emphasized the need for real leadership at the top and organizational talent to direct and manage the cultural diversity of the teams.
In addition to this de-facto beneficent and visionary scientific dictatorship the effort was backed by an equally powerful group of no-nonsense Hollywood-based founders who demanded accountability during the three-year grant, with the end result being some tangible improvement for patients.
During the American Association for Cancer Research Annual Meeting in April, the five dream teams came together during a session to discuss their work to date.
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Although perhaps premature to comment on the progress of their respective science, it became apparent that several of the presenters had undergone something of a cultural change fostered upon them by what Dr. Sharp called “shotgun marriages,” a reference to his Kentucky heritage, he noted.
He used the expression prior to introducing the dream team of “Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer,” co-led by Craig N. Thompson, MD, Director of the Abramson Cancer Center at the University of Pennsylvania, and Daniel D. Von Hoff, MD, Physician in Chief, Senior Investigator, and Director of the Clinical Translational Research Division at the Translational Genomics Research Institute (TGen), in Phoenix (see accompanying story.)
But Dr. Sharp's terminology also brought a broad smile to the face of Dennis Slamon, MD, PhD, another dream team co-leader who had just returned to the audience after providing information about his project (“An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and their ‘Resistance’ Phenotypes”) with co-leader Joe W. Gray, PhD.
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“Yes,” Dr. Sharp concurred during a telephone interview when asked whether Drs. Slamon and Gray were also hauled before the translational altar with the aid of some artful persuasion—“they were the other team that was merged, but all teams experienced some changes.”
Dr. Sharp said that he felt the new paradigm was working.
“I think we have been successful; at least it has exceeded my expectations, and I go into things pretty realistically. I think we had a bigger impact in the review process than I had anticipated. We came out with these very high-profile founders of SU2C who committed themselves almost totally to the effort and sent the message down to the system that said something needs to be done,” he said.
“As someone involved and committed to cancer research, to have that visible force up there has just been exhilarating because it's brought [this research] and these issues to the attention of the public now when the opportunities exist.
“The review process gave us a lot of flexibility in the sense that we had a diverse group of people sitting on the committee and had a number of strong personalities who weren't afraid to say this is the same old stuff, we shouldn't be going there, and let's do something different.”
He said the committee was very energized and engaged probably because it had more discretion making decisions about who to fund and how, and was very interactive with the groups submitting proposals.
“Among some of the marriages that I know of, we've already seen interactions that are changing the culture of the groups, and even if it doesn't translate in two years it's a wonderful outcome and will change everything in time,” he said.
‘Culture Eats Strategy’
Dr. Sharp said that immediately following the AACR session he attended a meeting for all the SU2C participants and noticed a banner set up by Laura Ziskin, one of Stand Up's co-founders, a member of its Executive Leadership Council, and the executive producer of both its original television “roadblock” broadcast in 2008 and its upcoming broadcast scheduled for Friday, Sept. 10 at 8 pm ET on ABC, NBC, CBS, as well as CNN, HBO, MTV, TBS, Discovery Health, TNT, and Bravo, and a possibility for other networks as well.
The banner read: “Culture eats strategy for lunch,” and Dr. Sharp said he was intrigued by its meaning, explaining that “although culture is often difficult to define, it's really very important that if you want to get something done, you have to have the right chemistry—and even if you don't have the right strategy at the beginning, you're still going to make the transitions you need to get to the end if the culture is right.”
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In fact he was so excited by the concept he said he was going to include it in a talk he was planning to give at MIT.
‘Chills Running Down My Spine’
He also said that he had “chills running down my spine” after coming out of AACR's opening plenary session on “Innovations in Translational Cancer Medicine.”
“I mean, to see these great clinical scientists and scientists being able to design around mutations and sensitivities, and to go from cells to patient responses is just thrilling. This is a new day in cancer therapy, and the whole thing is going to change. The cooperative groups and all the big bureaucracy at NCI will have to change, and it's going to change.”
He predicted that the pressure of this new science and the opportunities it will bring will lead to change and SU2C is providing a little glimpse of what may be possible under certain circumstances, including impacting regulations and how cancer treatments are developed.
“In terms of translation to clinical treatment, we are in the middle of a breakthrough of how it can be done and it's coming with personalized use of cancer treatments. Dan Von Hoff said people were calling him and said they wanted to get into his trial ‘not because you're going to help me, but because of what I can contribute’ [to the science].”
Dr. Sharp also emphasized SU2C's message that the effort was not just about finding cures but also about survivors having a good quality of life living with the disease.
Margaret Foti: NCI Interested in SU2C Process
AACR CEO Margaret Foti, PhD, said during a phone interview that she felt the term shotgun marriage was unfortunate since it didn't discuss the process or value, and that an enormous amount of the success was derived from Dr. Sharp's involvement in this project.
She added that the NCI has expressed interest in the process, and that the SU2C founders have said that if others take the model and use it effectively then they would be happy and would consider that a success.
“This has been a unique scientific partnership for AACR, which supports the scientific committee with staff in grants administration and management,” Dr. Foti said.
“Some very interesting synergies have been coming from the people working together who wouldn't have worked together before since they're from different institutions. The SU2C founders really hit it right when they said it would maximize team science and advances.”
Laura Ziskin: ‘50 Yards Down the Field’
Laura Ziskin told OT via phone that she considered Stand Up's effort to be “about 50 yards down the field.”
“Regarding the cultural shift we are about halfway there. We still have some obstacles. We're not sure we're translational enough and that we went far enough in that direction in doing what we can do to make translational models from bench to bedside to curbside.”
“Curbside,” she added, meant increasing access to cancer treatments, and that she hoped the new translational models could be applied to other diseases.
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Ms. Ziskin noted that in the time since OT's 2008 SU2C article was published, her breast cancer had returned, bringing a new sense of urgency to SU2C and providing her with a somewhat renewed perspective about the importance of living with and not dying from cancer—as evidenced by her getting married on her 60th birthday in March.
She reiterated that the Stand Up founders had viewed the promise of cancer research on a similar level as the Manhattan Project to create the first atomic bomb during World War II, or the race to the moon, or conquering polio or AIDS.
Ms. Ziskin recalled that at the very first SU2C ad hoc meeting, (the now deceased) Judah Folkman, MD, evoked patronage during the Renaissance when discussing the group's proposed funding model.
And she said that during other meetings with those being funded with Dream Team grants or recipients of SU2C's Innovative Research Grants Funding Early Career Scientists she learned that many of the researchers didn't even bother applying to NIH or NCI because they thought their ideas would be considered too innovative for funding.
“We gave Flip cams to them so they could communicate visually with the other teams—Maybe we [SU2C's founders] won't learn how to become scientists, but the researchers can learn to be filmmakers,” she said.
Sherry Lansing: ‘Power of the People’
Sherry Lansing, founder and chair of the Sherry Lansing Foundation, a co-founder and member of SU2C's Executive Leadership Council, and board chair of the Entertainment Industry Foundation that sponsors Stand Up, said that her colleagues started the effort with great passion and desire to change the paradigm of cancer research.
“We have all been touched by cancer or are struggling with it now. I've been a cancer advocate since my mother died 25 years ago, and we observed the silos and how the first floor didn't speak to the second floor, and how one hospital didn't speak with another hospital.
“We are in awe of the scientists, and none of this could be done without Phil Sharp and the committee he assembled, which is beyond reproach, as well as without AACR, or our donors.
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“I come from the stem cell board involved in the initiative in California where $3 billion was passed by the legislature through efforts driven by patient advocates. It was passed by the power of the people, and patient advocates can be a very strong group if they can harness their energy.
“Shotgun marriage or not, these people [award recipients] were energized by each other and could not stop talking about how much they enjoyed the process.”
Ms. Lansing said that since she and her SU2C colleagues came from outside the scientific establishment, they could be as idealistic as they wanted, and that although she is cautiously optimistic about eventual outcomes, so far she's thrilled with what has been taking place.
‘Shotgun Marriage’ Dream Team Enhanced by Scientific Coupling
The “shotgun marriage” that led to the teaming of proposals presented by Penn's Craig Thompson, MD, and TGen's Daniel Von Hoff, MD, created a sum greater than its parts.
In individual interviews with both co-leaders of the dream team involved in “Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer,” as well as with SU2C Scientific Advisory Committee Chair Phillip A. Sharp, PhD, OT learned a little about the dynamics behind this Dream Team's formation.
The team's goal is to develop tests using advanced imaging techniques to determine what nutrients fuel the growth and survival of pancreatic cancer cells. Based on findings that indicate that most cancer cells thrive on a continuous supply of glucose, the research will look at the possibility of starving cancer cells to death by depriving them of glucose, which could lead to developing more individualized treatments with fewer side effects.
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“Dan and Craig's work is showing progress,” said Dr. Sharp. “Both had very strong proposals going in on pancreatic cancer, with one [Craig Thompson] very strong into new insights in metabolism and the other [Dan Von Hoff] really strong in clinical translations that needed to get to new targets.”
Dr. Sharp also said that Dr. Von Hoff was intrigued by Dr. Thompson's integration of personal imaging with PET scans into his clinical trials.
“So we had to say, ‘Look folks, you're going to have to do it. We want you both together.’ And so they had to make some very tough changes that were cordially negotiated. They had legitimate complaints, since they had both developed teams and gotten ideas together and came in with very goodhearted and good proposals and then were told they'd have to change their teams and redesign everything, and boy, that's really hard to do and they found it difficult. I was aware that with big egos and the right insights into what had to be done, their commitment to others would increase.
“The two teams are beginning to click already and are having an impact on the clinical design and trials, and I'm very optimistic that good things will happen and five or 10 years from now those two will be changed by this experience.”
Honeymoon Still in Progress
According to the now-integrated team the honeymoon is still in progress.
“I think it was a very exciting learning process to go through and we were challenged by this grand experiment,” said Dr. Thompson. “We were honored that they [the Scientific Advisory Committee] thought our ideas were good, and saw that we had overlapping interests looking at different problems dealing with new approaches to tumor resistance.”
He said his original proposal was looking at both pancreatic and brain cancers from a more basic science approach, and that Dr. Von Hoff's team had put together a proposal from the opposite, clinical, side of the spectrum, and that the two teams might never have otherwise come together, since no mechanism had existed before that recognized the similarities and possibilities of pooling various expertise together.
Dr. Von Hoff said he was delighted to have been included as part of a dream team and never had any problems with the integration.
“When I found out [about the merging] my reaction was ‘this is terrific, where do I sign up?' It was a great opportunity to work with someone like Craig, with his intellect and scope of the biology of cancer, and his work is in a different area. We both knew that pancreatic cancer is a bad disease, and they did us a tremendous favor putting us together since we would have a better chance for success.”
He said that the committee's review process was one of the most grueling he had ever encountered and that it was also very difficult for him and Dr. Thompson to contact their collaborators on their original separate proposals and let them know their roles had changed or they would not be part of the final team.
The Dream Team has clinical trials under way, and with colleagues from Johns Hopkins, Princeton, and Salk, it expects that the efforts will be able to more than double what is currently a 20% annual survival rate for pancreatic cancer within the allotted three-year grant period.
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© 2010 Lippincott Williams & Wilkins, Inc.