SU2C’s Unique Research Funding Model Yielded Success With First Round of Dream Team Grants
WASHINGTON, D.C. — Stand Up To Cancer (SU2C) and the American Association for Cancer Research, SU2C’s scientific partner, are pleased to announce that the original Dream Team grants awarded by SU2C to five multi-institutional, cross-disciplinary research teams in May 2009, have accelerated cancer research progress that has been translated into meaningful advances for patients with cancer in just three years.
Focusing on epigenetic therapy; the PI3K pathway in women’s cancers; breast cancer; detection and analysis of circulating tumor cells; and pancreatic cancer, these original Dream Teams have made tremendous advances, including:
- A new potential treatment strategy whereby cancer patients receive two types of therapy sequentially because the first therapy, which is an epigenetic therapy that is a combination of two drugs, makes cancer cells more sensitive to the second;
- Numerous potential novel treatment options for women with breast cancer;
- The development of a new, noninvasive way to monitor cancer patients’ responses to treatments in real time; and
- The identification of a drug combination that extends the lives of patients with metastatic pancreatic cancer.
Judy DeMarsh, a 66-year old lung cancer patient and a nurse, is one person who has benefited from the new sequential treatment strategy that includes the epigenetic therapy developed by one of the Dream Teams. “Three years after being diagnosed with quite advanced cancer, and I’m still here and feeling great,” said DeMarsh. “The result is better than I could have imagined. I know it’s science, but it feels like a fairy tale, and hopefully other patients will be more encouraged not to give up and to participate in clinical trials. I give my heartfelt thanks to SU2C for funding the epigenetic therapy, to the team of researchers that developed it, and to those researching and developing the immunotherapy.”
In addition to promoting immense scientific and clinical progress, the establishment of the SU2C Dream Teams has shifted the way much clinical cancer research is conducted. Not only are formerly competitive researchers and institutions collaborating, but the “Targeting the PI3K Pathway in Women’s Cancers” Dream Team brokered a rare partnership between pharmaceutical companies: Novartis and AstraZeneca agreed to join forces with the Dream Team and assess the effectiveness of a combination of investigational anticancer drugs, helping achieve SU2C’s goal of getting new treatments to patients faster.
SU2C’s distinctive Dream Team approach to funding cancer research was specifically designed to eliminate barriers to creativity and collaboration, in part, by enabling scientists with different expertise from different institutions across the country — and in some cases, internationally — to work together. Each Dream Team project is translational in nature, designed to move science from “bench to bedside,” where it can benefit patients, as quickly as possible.
A key attribute of the Dream Team funding model is that each Dream Team’s progress is evaluated biannually by a group of three reviewers, typically members of the SU2C Scientific Advisory Committee (SAC) that reviewed the initial Dream Team applications and made recommendations on funding to SU2C. The purpose of these periodic reviews is to ensure that milestones and objectives are being satisfactorily achieved. These reviews also provide a unique level of interactivity between grant recipients and members of the Nobel laureate-led oversight committee that has been pivotal in the successes that the Dream Teams have achieved.
“The unprecedented, collaborative research enabled by Stand Up To Cancer’s Dream Team grants has helped patients in the way that we hoped it might,” said Nobel Laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology in Boston, Mass., who chairs the SAC. “The five original Dream Teams are to be commended on the way that they executed their mission with a laser-like focus that allowed them to take scientific advances into the clinic at an extraordinarily quick pace. The fact that the work of these teams of researchers led to the initiation of more than 40 clinical trials over the course of just three years is unparalleled.”
“This is a significant milestone for us, and we are incredibly grateful to everyone who so generously contributed in order to make this happen,” said Sherry Lansing, SU2C co-founder, chairperson of the Entertainment Industry Foundation’s (EIF) Board of Directors and founder of the Sherry Lansing Foundation. “It is truly inspirational to see that the dedication of — and collaboration within — these five teams of incredible scientists has already paid off for patients. It motivates us to work harder in our mission to support this innovative way of promoting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated time frame.”
The original five SU2C Dream Teams are comprised of seven leaders, three co-leaders and 27 principal researchers from more than 40 institutions, with more than 220 individuals participating in total. Each team has at least two members from patient advocacy groups to ensure that the perspectives of the patients and survivors they represent are integrated into the research on an ongoing basis.
The total funding level for the five teams’ first three years of work was $73.6 million. At the recommendation of the SAC, an additional $7.2 million in total funding is being provided to four of these five teams, and the time frames for all of the teams have been extended, by either one or two years.
The teams and the important topics they are pursuing are listed below in alphabetical order according to the leaders’ names:
- “Bringing Epigenetic Therapy to the Forefront of Cancer Management.” Leader: Stephen B. Baylin, M.D., deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Co-leader: Peter A. Jones, Ph.D., D.Sc., distinguished professor of urology, and biochemistry and molecular biology at the University of Southern California Norris Comprehensive Cancer Center;
- “Targeting the PI3K Pathway in Women’s Cancers.” Leader: Lewis C. Cantley, Ph.D., director of the Cancer Center at Beth Israel Deaconess Medical Center; Co-leader: Gordon B. Mills, M.D., Ph.D., chair of the Department of Systems Biology at The University of Texas MD Anderson Cancer Center;
- “An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their ‘Resistance’ Phenotypes.” Leaders: Joe W. Gray, Ph.D., chair of the Department of Biomedical Engineering at Oregon Health & Science University, and Dennis J. Slamon, M.D., Ph.D., director of clinical/translational research at UCLA’s Jonsson Comprehensive Cancer Center;
- “Bioengineering and Clinical Applications of Circulating Tumor Cell Chip.” Leader: Daniel A. Haber, M.D., Ph.D., director of the Massachusetts General Hospital Cancer Center; Co-leader: Mehmet Toner, Ph.D., professor of biomedical engineering at Harvard Medical School; and
- “Cutting Off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer.” Leaders: Craig B. Thompson, M.D., president and chief executive officer, Memorial Sloan-Kettering Cancer Center, and Daniel D. Von Hoff, M.D., distinguished professor and physician-in-chief, The Translational Genomics Research Institute (TGen).
Descriptions of each Dream Team’s work and progress during the initial three-year grant term follow.
In many cases, the genetic alterations that drive cancerous cell behaviors work in conjunction with changes in what is known as the cell’s epigenome. The epigenome is the sum of all the chemical, or epigenetic, flags on a cell’s genome that help control whether a gene is turned on or off.
The positioning of epigenetic flags on the genome is not permanent, so it should be possible to reverse the abnormal positioning of epigenetic flags seen in cancer. The overarching goal of the Epigenetic Dream Team was to pursue the exciting potential of attacking cancers using therapies that overturn the epigenetic abnormalities that inappropriately turn genes on or off in cancer cells, thus bringing the promise of epigenetic therapy to the clinic for the benefit of patients with different types of cancer.
In its first three years of funding, this Dream Team initiated five clinical trials. These have yielded impressive results for early-stage clinical trials, with vigorous clinical responses with minimal toxicities observed for several patients. They have also identified a novel therapeutic approach that has the potential to change the face of therapy for tens of thousands of cancer patients. The Dream Team is currently in the final stages of designing later-stage trials to validate this novel treatment strategy.
The potential new therapeutic approach is to treat patients with an epigenetic therapy, or a combination of two epigenetic therapies, and then with a conventional chemotherapy or an experimental immunotherapy.
The idea for this unique approach came from observations from one of the phase I/II clinical trials conducted by the Epigenetic Dream Team that suggested that epigenetic therapies can make patients’ tumors more sensitive to subsequent treatments. Specifically, these data showed that a substantial number of patients with recurrent, metastatic, non–small cell lung cancer who did not respond to treatment with the combination epigenetic therapy being tested in the trials, did respond dramatically to subsequent chemotherapy or experimental immunotherapy. The responses observed were far more extensive and durable than expected for patients with advanced, non–small cell lung cancer who had not benefited from previous treatments. Therefore, epigenetic therapy may be used to sensitize cancers for subsequent therapies.
In a first-in-human phase I/II clinical trial conducted by the Epigenetic Therapy Dream Team, a novel epigenetic therapy called SGI-110 has shown promise as a new treatment option for patients with an early form of leukemia, myelodysplastic syndrome, and those with acute myelogenous leukemia.
Aaron Cohen, a 77-year-old acute myeloid leukemia patient, received SGI-110 through the Epigenetic Dream Team clinical trial. “I’ve had a good life, and if this was what God wanted I was OK with it,” Cohen said of his diagnosis. “I was in the process of tidying everything up in my life when I went on the trial. Now my outcome looks wonderful and my outlook on life has changed. I can’t thank the doctors enough. For me, this drug has been a lifesaver.”
The phosphatidylinositide 3 kinase (PI3K) pathway is a complex signaling pathway that, in concert with other signaling pathways, regulates cell survival and growth. Genetic mutations that lead to inappropriate PI3K pathway activity are the most frequently detected cancer-driving mutations in women’s cancers, in particular breast, ovarian and endometrial cancers.
A number of drugs that inhibit the PI3K pathway were developed and are currently in clinical trials. However, only a fraction of patients who enroll in these trials benefit, and it has not been possible to predict which patients will respond positively.
The goal of the PI3K Pathway in Women’s Cancers Dream Team was to discover approaches that could predict which patients with breast, ovarian or endometrial cancer will respond positively to PI3K inhibitors.
In its first three years of funding, this Dream Team initiated or participated in 12 clinical trials testing PI3K-targeted therapies as single agents or as part of a combination therapy, and more than 600 patients have been enrolled in these trials to date. One of these clinical trials has provided hope that the SU2C Dream Team model of team science can transform how cancer research is done, by stimulating collaboration between pharmaceutical companies to reduce the length of time it takes to test new therapies in the clinic.
This ongoing phase I clinical trial involves testing a combination of two investigational drugs being developed by different pharmaceutical companies — Novartis’ PI3K inhibitor BKM120 and AstraZeneca’s olaparib, an inhibitor of poly-(ADP-ribose) polymerase (PARP) — in patients with recurrent, triple-negative breast cancer or recurrent, high-grade serous ovarian cancer.
The Dream Team successfully negotiated this collaboration between Novartis and AstraZeneca after generating robust preclinical data suggesting that the combination of BKM120 and olaparib would greatly benefit women with certain types of breast and ovarian cancers.
After the PI3K Pathway in Women’s Cancers Dream Team generated data indicating that breast cancers expressing the estrogen receptor, a hormone receptor involved in driving the growth of these breast cancers, frequently had mutations in a gene tied intimately to the PI3K pathway, the PIK3CA gene, the Dream Team initiated another phase I clinical trial. Currently under way, this clinical trial, testing a combination of BKM120 and letrozole, a drug already used for the treatment of local or metastatic breast cancer that is hormone-receptor positive, is showing promise for postmenopausal patients with hormone receptor-positive, metastatic breast cancer, particularly those whose tumors have PIK3CA mutations.
During the past few years, it has become clear that breast cancer is not a single disease, but a spectrum of diseases that vary in their biology and response to treatment. The three main subtypes of breast cancer are:
- Hormone receptor-positive breast cancer, which includes all breast cancers expressing either, or both, of the hormone receptors (estrogen receptor and progesterone receptor);
- HER2-positive breast cancer, which includes all breast cancers in which the HER2 gene is amplified; and
- Triple-negative breast cancer, which includes all breast cancers that lack expression of the estrogen receptor, the progesterone receptor and HER2.
As a result of these discoveries, treatment for breast cancer has moved beyond a one-size-fits-all approach to an era in which it is tailored to the biology of a patient’s cancer, as determined by breast cancer subtype. Despite this, many breast cancers eventually develop ways to outsmart these new tailored treatments and are said to have become drug-resistant.
The goal of the Breast Cancer Dream Team was to identify molecular mechanisms that lead to drug resistance in the three major breast cancer subtypes and to identify and validate new drug combinations and targets that can be pursued in clinical trials.
In its first three years of funding, this Dream Team conducted preclinical work that led to the initiation of nine clinical trials.
For example, preclinical work by the Dream Team led to the idea that the effectiveness of the drug letrozole, which is used for the treatment of local or metastatic breast cancer that is hormone-receptor positive, might be enhanced by adding the investigational agent PD 0332991, which is being developed by Pfizer, to the treatment regimen.
Recently reported results of the phase II clinical trial of the PD 0332991 and letrozole combination indicated that it provided meaningful benefit to women with advanced, estrogen receptor-positive breast cancer. The combination significantly improved median progression-free survival compared with treatment with letrozole alone: 26.1 months for those receiving the combination versus 7.5 months for those receiving letrozole alone.
A phase III clinical trial testing this combination in patients with advanced estrogen receptor-positive breast cancer was initiated by Pfizer in early 2013.
In addition to being involved in preclinical work resulting in numerous clinical trials, the Breast Cancer Dream Team has undertaken a tremendous bioinformatics effort to integrate a cornucopia of genomic data generated not only by this Dream Team, but by other Dream Teams as well. This initiative has revealed genomic signatures related to drug sensitivity and resistance, as well as prognosis for the three major breast cancer subtypes, suggesting ways to link drugs to cancers with specific genomic signatures.
Bioengineering and Clinical Applications of Circulating Tumor Cell Chip
Cancers arise within the cells of an organ, such as the breast or pancreas, but predominantly cause death by entering the bloodstream, disseminating throughout the body and spreading — or metastasizing — to the bone, liver, lungs or brain.
Cancer cells that spread from the primary tumor can be found in the blood of patients with cancer. These circulating tumor cells (CTCs) are extraordinarily rare — one per one billion normal cells. The ability to detect and analyze them would allow significant advances in detecting and treating cancers as well as understanding the fundamental mechanisms by which cancers spread.
The goal of the CTC-Chip Dream Team was to develop a noninvasive technology sensitive and reliable enough for physicians to use in the clinic to make cancer treatment decisions.
In its first three years of funding, this Dream Team developed a technology that has the potential to revolutionize the ways in which cancers are detected and treated.
The technology is a third-generation microfluidic chip that can isolate CTCs more rapidly and from larger volumes of blood compared with the first- and second-generation models they constructed. In addition, this third generation CTC-Chip, called the CTC-iChip, works in a way that makes the isolated tumor cells available for a wider array of subsequent scientific analyses, providing the possibility of enhanced clinical investigation and potentially leading to improved clinical care for patients with cancer.
In addition, the Dream Team has used the second-generation CTC-Chip in several clinical trials to generate clinical data indicating that this technology could make it possible to noninvasively analyze cancers of the internal organs, including lung, prostate, breast and pancreatic cancers, both at the time of diagnosis and throughout treatment. This would enable clinicians to better match patients to effective therapies and monitor response to treatments.
The second-generation CTC-Chip also provided the Dream Team the opportunity to conduct groundbreaking clinical investigation. Using the technology, the Dream Team have gained new understanding of the mechanisms by which breast cancers metastasize, providing potential biomarkers of disease progression.
The CTC-iChip is being developed in conjunction with Johnson & Johnson.
As the fourth leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. More than 80 percent of patients die within the first year of diagnosis. Recent advancements have had little impact, and a new approach is desperately needed.
Most cancer cells are addicted to a continual supply of specific nutrients to produce the energy they need for growth and survival. Researchers have suggested the possibility of “starving” cancer cells to death by depriving them of the nutrients they require for survival and growth.
The overall goal of the Pancreatic Cancer Dream Team was to improve survival for patients with advanced, metastatic pancreatic cancer by first identifying the nutrients pancreatic cancer cells require to fuel their growth and survival, and then developing ways to cut off the fuel supplies.
In its first three years of funding, this Dream Team designed and implemented a series of clinical trials testing a drug being developed by Celgene Corporation, a special form of the drug paclitaxel — nanoparticle paclitaxel (Abraxane). The impressive results of the phase III clinical trial were released in January 2013: Patients with metastatic pancreatic cancer receiving the investigational drug in combination with the standard-of-care chemotherapy gemcitabine lived significantly longer than those receiving gemcitabine alone.
In the phase III clinical trial, the investigational drug combination resulted in a 59 percent increase in one-year survival compared with gemcitabine alone (35 percent vs. 22 percent). It also more than doubled two-year survival (9 percent vs. 4 percent). In addition, in the earlier-stage clinical trials the Dream Team observed that the investigational drug combination caused high rates of tumor shrinkage and this enabled patients who had not been able to have potentially curative surgery to have that surgery.
The Dream Team also developed a novel approach to analyzing pancreatic cancer. Using biopsies from tumors removed during surgery, they have identified new metabolic pathways (fuel supplies) involved in tumor growth that represent potential new therapeutic targets.
Stand Up To Cancer’s major contributors include founding donor Major League Baseball, which has committed more than $30 million and provides countless opportunities to build the Stand Up To Cancer grassroots movement by encouraging fans all over the country to get involved; and Sidney Kimmel, the country’s largest individual contributor to cancer research. Other major SU2C donors include Bloomberg Philanthropies, Cancer Research Institute, Cancer Treatment Centers of America, Genentech, MasterCard, Melanoma Research Alliance, Prostate Cancer Foundation, The Safeway Foundation, Sean Parker Foundation, St. Baldrick’s Foundation, Wallis Annenberg and The Annenberg Foundation, Amgen, GlaxoSmithKline, Pfizer, Oakland A’s Owner/Managing Partner Lew Wolff, Comcast, Inter-American Development Bank (IDB), Philips Electronics, Steve Tisch, The Island Def Jam Music Group and many others.
About Stand Up To Cancer
Stand Up To Cancer (SU2C) – an initiative of the Entertainment Industry Foundation, a 501(c)(3) non-profit organization – raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. SU2C marshals the resources of the media and entertainment industries in the fight against this disease.
Current members of the SU2C Council of Founders and Advisors (CFA) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation’s Board of Directors and Founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer’s In-house Production Team, and Nonprofit Executive Ellen Ziffren. All current members of the CFA were co-producers of the 2012 televised special. The late co-founder Laura Ziskin executive produced both the Sept. 5, 2008, and Sept. 10, 2010, broadcasts. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D., R.N., has served as SU2C’s president and CEO since 2011.
SU2C’s “Dream Team” approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed “too risky” by conventional funding sources. One hundred and one institutions are currently involved. As SU2C’s scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.
Stand Up To Cancer
Jane E. Rubinstein
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American Association for Cancer Research