HIGHLIGHTS• Combining vitamin C with a demethylating agent in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) may improve the therapy’s ability to combat cancers. At this point, this effect has only been shown in cell lines, and the efficacy in patients can only be confirmed by conducting a rigorous and controlled clinical trial. • A pilot clinical trial is underway to investigate the safety and effectiveness of this therapy. If successful, investigators plan to pursue further clinical studies.• The investigators urge patience and caution patients to wait for the results of the clinical trial.
Newswise — GRAND RAPIDS, Mich. (August 29, 2016)—A simple adjustment to patients’ therapeutic regimen may improve the effectiveness of the standard epigenetic treatment for myeloid dysplastic syndrome (MDS) and acute myeloid leukemia (AML).New findings published today in the Proceedings of the National Academy of Sciences showed in lab studies that supplementing an epigenetic cancer drug called decitabine with vitamin C enhanced the drug’s ability to impede cancer cell growth and trigger cellular self-destruction in cancer cell lines. A pilot clinical trial based on this work is ongoing in adult patients with MDS or AML at Rigshospitalet in Copenhagen, Denmark. It combines a similar drug called azacitidine —the standard of care therapy—with vitamin C. Many cancer patients are deficient in vitamin C; the proposed approach seeks to correct this deficiency rather than overload patients with the vitamin.“If the pilot trial is successful, we plan to pursue a larger trial to explore this strategy’s potential as a straightforward and cost-effective way to improve the existing therapy for AML and MDS,” said Peter Jones, Ph.D., D.Sc., co-senior author of the PNAS study, chief scientific officer at Van Andel Research Institute (VARI) and co-leader of the Van Andel Research Institute–Stand Up To Cancer (VARI–SU2C) Epigenetics Dream Team. “At the same time, we must urge patience and caution. Only a clinical trial that combines azacitidine with the blinded addition of either vitamin C or a placebo will give the true answer as to whether or not vitamin C increases the efficacy of azacitidine in patients. We must emphasize that our trial is limited to a certain subset of patients with MDS or AML on a specific therapeutic regimen. We do not have evidence that this approach is appropriate for other cancers or chemotherapies.”The proposed strategy reflects a continuing move toward combination therapies, particularly when it comes to epigenetic approaches, which target the mechanisms that control whether genes are switched “on” or “off.” In cancer, these switches inappropriately activate or silence important genes, such as those that regulate cell growth and life cycle, ultimately leading to tumors. Epigenetic therapies are thought to work in two ways to fix these errors in cancer cells—by correcting the “position” of the gene switches and by making the cell appear as though it’s infected by a virus, triggering the immune system.The trial is led by Kirsten Grønbæk, M.D., DMSc., chief hematologist and professor at University of Copenhagen’s Rigshospitalet and member of the VARI–SU2C Epigenetics Dream Team, which is supporting the trial and associated research. It will include 20 patients; preliminary results are expected by spring or summer 2017.“This type of combination therapy is promising but more work is needed to determine its safety and efficacy,” Grønbæk said. “It is truly exciting to consider that there could be a simple and elegant approach to help patients fight MDS and AML. However, as a physician, I strongly urge patients to wait for the results of the clinical trial and to discuss all dietary and supplemental changes with their doctors.”An estimated 13,000 people in the U.S. are diagnosed with MDS annually and about 20,000 are diagnosed with AML. Currently, only about half of patients with MDS and AML respond to the epigenetic therapy alone.The research reported in the paper was conducted by Grønbæk and Jones' teams in collaboration with Gangning Liang, M.D., Ph.D., at University of Southern California’s Keck School of Medicine, and Stephen Baylin, M.D., co-leader of the VARI-SU2C Epigenetics Dream Team and co-head of Cancer Biology at Johns Hopkins University’s Sidney Kimmel Comprehensive Cancer Center. It is supported by the VARI–SU2C Epigenetics Dream Team, the National Cancer Institute, the Vicky Joseph Cancer Research Fund, the Novo Nordisk Foundation, the Danish Cancer Society and the Lundbeck Foundation.
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Liu M, Ohtani H, Zhou W, Ørskov AD, Charlet J, Zhang YW, Shen H, Baylin SB, Liang G*, Grønbæk K*, Jones PA*. In press. Vitamin C increases viral mimicry induced by 5-aza2’-deoxycytidine. Proc Natl Acad Sci U S A.*Co-senior authors
ABOUT THE VAN ANDEL RESEARCH INSTITUTE–STAND UP TO CANCER EPIGENETICS DREAM TEAMThe Van Andel Research Institute–Stand Up To Cancer (VARI–SU2C) Epigenetics Dream Team fosters collaboration between several of the world’s most respected research and clinical organizations in an effort to translate scientific discoveries into new standards of patient care. The goal is simple—get new and more effective cancer therapies to patients faster.
The VARI–SU2C Epigenetics Dream Team was established in 2014 and builds on the foundations laid by the first iteration of the SU2C Epigenetics Dream Team, which was founded in 2009. Today’s team is based at Van Andel Research Institute in Grand Rapids, Michigan, and is led by the Institute’s Chief Scientific Officer Peter Jones, Ph.D., D.Sc., and Stephen Baylin, M.D., VARI professor and co-head of Cancer Biology at Johns Hopkins University’s Sidney Kimmel Comprehensive Cancer Center. The team includes leading scientists and clinicians with vast experience in translating basic science and promising therapies from the lab to the clinic.
The team is honored to be affiliated with Stand Up To Cancer, a program of the Entertainment Industry Foundation. Launched in 2008, SU2C draws on the resources of the entire entertainment industry to encourage the public to support research conducted by teams of scientists, as well as by individual investigators. To date, more than 1,100 researchers from more than 130 institutions in seven countries have collaborated across SU2C’s 19 Dream Teams, six Translational Research Teams and 36 Innovative Research Grants.
Rigorous and objective scientific oversight and review is provided by SU2C’s scientific partner, the American Association for Cancer Research (AACR), the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer.
ABOUT VAN ANDEL RESEARCH INSTITUTEVan Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 360 scientists, educators and staff. Van Andel Research Institute (VARI), VAI’s research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson’s and other diseases and translating those findings into effective therapies. The Institute’s scientists work in onsite laboratories and participate in collaborative partnerships that span the globe. Learn more about Van Andel Institute or donate by visiting www.vai.org. 100% To Research, Discovery & Hope®
ABOUT STAND UP TO CANCERStand Up To Cancer® (SU2C) raises funds to accelerate the pace of research to get new therapies to patients quickly and save lives now. SU2C, a program of the Entertainment Industry Foundation (EIF), a 501(c)(3) charitable organization, was established in 2008 by film and media leaders who utilize the industry’s resources to engage the public in supporting a new, collaborative model of cancer research, and to increase awareness about progress being made in the fight against the disease. As SU2C’s scientific partner, the American Association for Cancer Research (AACR) and a Scientific Advisory Committee led by Nobel Laureate Phillip A. Sharp, Ph.D., conduct rigorous, competitive review processes to identify the best research proposals to recommend for funding, oversee grants administration, and provide expert review of research progress.
Current members of the SU2C Council of Founders and Advisors (CFA) include Katie Couric, Sherry Lansing, Lisa Paulsen, Rusty Robertson, Sue Schwartz, Pamela Oas Williams, Ellen Ziffren, and Kathleen Lobb. The late Laura Ziskin was also a co-founder. Sung Poblete, Ph.D., R.N., has served as SU2C’s president since 2011.
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