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Illustration 1. David Weinstock, MD, and colleagues are investigating genetic risk factors for leukemias and lymphomas. Pictured from left to right are Nadja Kopp, MS; Akinori Yoda, PhD; Oliver Weigert, MD; and Dr. Weinstock.

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When the first “Stand Up To Cancer” (SU2C) live, celebrity-filled fundraising event was televised on all 3 major networks simultaneously across the United States in 2008, the organization started a movement to accelerate translational research.

Since then, it has raised approximately $180 million, awarding $73.6 million to 5 multidisciplinary “dream teams” that bring together more than 200 researchers from more than 50 institutions. In addition, it has awarded $9.6 million to 13 innovative research grant (IRG) recipients in their pursuit of high-risk innovative projects that may not otherwise receive funding. At press time, SU2C was preparing to announce another round of IRGs.

“Funding for each dream team was designed to be enough money for each team to move the needle in terms of patient-oriented accomplishments,” says Sung Poblete, PhD, director of clinical and translational programs for the American Association for Cancer Research (AACR),SU2C's scientific partner. “The review process is quite rigorous, and each dream team has detailed milestones it is required to meet in order to receive the second and third installments of its grant.”

SU2C was co founded by a number of women in the entertainment industry, including broadcaster Katie Couric and film executive Sherry Lansing. AACR administers the grants and provides scientific oversight in conjunction with the SU2C scientific advisory committee, led by Nobel Laureate Philip Sharp, PhD, institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology in Boston, Massachusetts. The committee makes recommendations concerning research priorities. Current SU2C projects address a wide range of cancer types and organ sites, including lung, ovarian, and breast cancers; leukemias and lymphomas; and difficult-to-treat cancers affecting children and young adults. In addition to the first televised fundraiser, SU2C held another in September 2010, sponsors an online support community and magazine, and conducts a public awareness campaign to support its efforts.

Breast Cancer Resistance to Targeted Drugs

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  2. Breast Cancer Resistance to Targeted Drugs
  3. Leukemia and Lymphoma Growth
  4. Current and Future Efforts

One of the 5 dream teams, which focuses on breast cancer, is cochaired by Joe Gray, PhD, a lead scientist with the Oregon Health and Science University Knight Cancer Institute in Portland, Oregon, and Dennis Slamon, MD, PhD, director of clinical/translational research at the University of California at Los Angeles Jonsson Comprehensive Cancer Center in Los Angeles, California. Their team is studying 3 breast cancer subtypes to understand how they become resistant to targeted drugs. They are evaluating new drugs and drug combinations to determine which ones should be tested on patients with specific subtypes in clinical trials.

Dr. Gray believes the dream team concept is important because of the many types of scientists who are working together versus competitively to search for answers. “It's imperative that we work collaboratively across multiple disciplines to really rapidly move things from the discovery phase all the way into the clinic,” he says. “The duration and expectations and scrutiny of the dream teams is quite high, and it really is motivating to everybody to work together to make progress more rapidly than we normally do.” The breast cancer dream team's 3-year, $16.5-million grant involves scientists from 13 institutions ranging from clinicians and statisticians to biologists and engineers. They are divided among 5working groups including triple negative breast cancer, estrogen receptor-positive breast cancer, human epidermal growth factor receptor 2-positive breast cancer, biological models of breast cancer, and discovery and computational biology.

Researchers are searching for the “driver genes” for these cancers as well as for ways to convey their findings to clinicians so clinical trials can be designedmore quickly. “In breast cancer,we have a lot of approaches that work for a while, but especially in metastatic disease, they stop working,” Dr. Gray says. “We want to determine the resistance mechanisms and then use the information to select therapies that will be particularly effective against genomic subsets.”

The team is developing an easily accessible database that integrates all existing information regarding breast cancer. This discovery platform will enable researchers to identify and validate new drug combinations and targets for clinical trials. It does so by combining the technology of 2 programs: Oncomine and the Cancer Genome Browser Web site. Oncomine combines all published information concerning breast cancer (and other cancers) in a way that enables comparison of data sets. Meanwhile, the genome browser Web site allows this information to be easily accessed on the Internet. The data that the team generates will be available through this mechanism to all its members and eventually to scientists and the public at large.

“What we're trying to do is lower the barrier to finding information that's already been generated,” Dr. Gray notes. “We have tens ofmillions of pieces of information on every cancer, and now the cancer genome browser makes it more straight forward.”

Team members are also working on ways to develop better models for cancer in the laboratory, models that would accurately represent what happens in the clinic. “There are thousands of agents to consider against breast cancer, but we can't test all of them in clinical trials,” Dr. Gray explains.“We need to figure out how to build better models and how to use them to develop better therapeutic strategies, whether it's by testing drugs on them or by attacking genomes with powerful, genome-wide cocktails to determine the weaknesses in the tumors.”

Key Points

  • SU2C has awarded $73.6 million to 5 multidisciplinary dream teams and $9.6 million to 13 IRG recipients with the goal of accelerating translational research.

  • The breast cancer dream team is developing an easily accessible database that integrates all existing information regarding breast cancer and will enable researchers to identify and validate new drug combinations and targets for clinical trials.

  • The team also is working on ways to develop better models for cancer in the laboratory to develop better therapeutic strategies.

  • One SU2C IRG is funding efforts to identify alterations in 22 leukemia and lymphoma subtypes, to confirm the alterations are making cells grow abnormally, and to determine how commonly they occur among the many types of blood cancers.

Although Dr. Gray does not know the status of SU2C funding for the team once their 3-year grant cycle is complete, he says they already are thinking about how to continue their collaborations. “They've been quite valuable, and the longer we work together, the more powerful it becomes,” he says.

Leukemia and Lymphoma Growth

  1. Top of page
  2. Breast Cancer Resistance to Targeted Drugs
  3. Leukemia and Lymphoma Growth
  4. Current and Future Efforts

Meanwhile, David Weinstock, MD, assistant professor of medicine in the medical oncology service at Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues are busy trying to determine genetic alterations that promote the growth of specific leukemias and lymphomas and that can provide new targets for treatment. He is the recipient of 1 of the 13 SU2C IRGs, for which he received $750,000 over 3 years.

What we're trying to do is lower the barrier to finding information that's already been generated. We have tens of millions of pieces of information on every cancer, and now the cancer genome browser makes it more straight forward.—Joe Gray, PhD

The distinction between a SU2C IRG and a more traditional funding mechanism such as a National Institutes of Health Research Project Grant (RO1) is that it enables him to focus on experiments that have more risk but potentially much greater reward, Dr. Weinstock notes.Dr. Weinstock's research focuses on functional genomics for hematologic malignancies and alterations rather than traditional sequencing. Specifically, the SU2C funding is supporting his efforts to identify alterations in 22 leukemia and lymphoma subtypes, to confirm that the alterations are capable of making cells grow abnormally and to determine how commonly they occur among the many types of blood cancers.

Dr. Weinstock and colleagues, including OliverWeigert, MD, and Akinori Yoda, PhD, developed a system that enables them to analyze large numbers of tumor specimens to find cancer-promoting alterations. Using that method, they discovered a protein called cytokine receptor-like factor 2 (CRLF2) that is over expressed in approximately 15% of adult and high-risk pediatric B-cell acute lymphoblastic leukemias. They also found that cells dependent on CRLF2 signaling are sensitive to small molecule inhibitors of either Janus kinases (JAKs) or protein kinase C family kinases.

As a result, their discovery, along with additional gene discoveries by scientists at other institutions, led to a Children's Oncology Group phase 1 clinical trial of JAK2 inhibitors within 2 years of CRLF2's identification.

“For the physician, it's really frustrating dealing with patients with rare diseases that don't get studied and have a terrible prognosis,” notes Dr. Weigert,who is helping refine the laboratory's screening methods to find more gene alterations. “That'swhywe felt this was an area in which we could make a huge impact.”

The group has identified multiple somatic mutations with the goal of trying to determine those that are key and can be translated quickly to animal models. Dr. Weinstock says they would not have been able to be as aggressive in their work without the SU2C funding. “Two things really give me goose bumps,” he says. “The first is actually seeing something we've discovered applied to human beings, and the second is the moment of that first discovery of a new cancer gene waiting to be sequenced and knowing we'll be the first humans on earth to know what that gene is.”

Current and Future Efforts

  1. Top of page
  2. Breast Cancer Resistance to Targeted Drugs
  3. Leukemia and Lymphoma Growth
  4. Current and Future Efforts

SU2C's fundraising and awareness efforts are ongoing, Dr. Poblete notes. At the end of 2010, for example, the organization and MasterCard joined forces with the Times Square Alliance and nearly 100 businesses in the Times Square area of NewYork City, with MasterCard donating $1 to SU2C every time a consumer used a MasterCard at a participating merchant. That effort raised approximately $1.5 million.

The organization also recently optioned the filmand television rights for The Emperor of Al lMaladies, the “biography of cancer” named one of 2010's top 10 books by The NewYork Times. SU2C is exploring producing a documentary series based on the book.

Because the organization is only 3 years old, Dr. Poblete says it is too soon to predict its long-term impact. “Funds for this type of work—projects undertaken by interinstitutional, multidisciplinary teams focused on accelerating the pace at which new treatments are broadly available—are relatively scarce,” he says. “That's the key challenge to seeing that more of it gets done.”