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Van Andel Research Institute–Stand Up To Cancer Epigenetics Dream Team

Overview

Finding the cancer therapies of tomorrow requires visionary thinking and innovative research today. The 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.

What are epigenetics? Why study it?

If the genetic code is a musical score, then epigenetics represents the various ways in which it may or may not be played. Although the actual notes on the sheet music do not change, the choice of tempo, instrument, volume and even the omission of parts of the piece alters what the listener hears. In much the same way, epigenetic modifications do not change the DNA sequence—which is virtually identical in all cells in a person’s body—rather, they regulate how the DNA is expressed. Epigenetics control how the DNA is used, switching particular genes “on” or “off” to determine cell type and function.
In the majority of human cancers, there are errors in the genome and the epigenome and these errors can contribute to cancer development, growth and treatment resistance. Identifying and understanding how these errors arise and how to correct them holds great promise for developing new, more effective therapies.

About the team

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.

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VARI-SU2C Epigenetics Dream Team members

Peter Jones, Ph.D, D.Sc. (Dream Team co-leader)
Chief Scientific Officer
Van Andel Research Institute

Stephen Baylin, M.D. (Dream Team co-leader)
Co-head of Cancer Biology; Virginia and D.K. Ludwig Professor for Cancer Research, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Professor, Van Andel Research Institute

Anthony El-Khoueiry, M.D.
Associate Professor of Clinical Medicine, Clinical Instructor—Division of Medical Oncology
University of Southern California

Kirsten Grønbæk, M.D., D.M.Sc.
Professor, Chief Physician
University of Copenhagen/Rigshospitalet

Jean-Pierre Issa, M.D.
Director—Fels Institute for Cancer Research and Molecular Biology
Temple University/Fox Chase Cancer Center

Patricia Kropf, M.D.
Deputy Director, Bone Marrow Transplant Program
Temple University/Fox Chase Cancer Center

Feyruz Rassool, M.D.
Associate Professor
University of Maryland School of Medicine

Charles Rudin, M.D., Ph.D.
Chief—Thoracic Oncology Service
Memorial Sloan Kettering Cancer Center

Ongoing VARI–SU2C Epigenetics Dream Team trials

Below is information about ongoing VARI-SU2C Epigenetics Dream Team trials. Please note, although Van Andel Research Institute is involved in clinical trials, the Institute does not treat patients nor are trials conducted onsite. Information about additional clinical trials beyond those conducted by VARI-SU2C Epigenetic Dream Team members can be found at clinicaltrials.su2c.org.

Metastatic colorectal cancer

Metastatic colorectal cancer
Metastatic colorectal cancer is the second leading cause of cancer death in men and women combined in the U.S.

What is being tested?
Resistance is a common problem in cancer treatment. It occurs when a person’s cancer stops responding to existing medications and therapeutic strategies. This trial investigates whether combining an epigenetic drug called guadecitabine with a standard treatment, irinotecan, can reverse resistance to irinotecan.

Trial details
Trial name: Phase I study of SGI-110 with irinotecan followed by randomized phase II study of SGI-110 with irinotecan versus regorafenib or TAS-102 in previously treated metastatic colorectal cancer
ClinicalTrials.gov numberNCT01896856
Status: Currently recruiting
Trial locations:

  • Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland
  • University of Southern California, Los Angeles, California
  • Memorial Sloan Kettering Cancer Center, New York, New York
  • VU University Medical Center, Amsterdam, The Netherlands

Industry partner: Astex Pharmaceuticals, Inc. 

For a list of inclusion and exclusion criteria and contact information for individual trial sites, please visit clinicaltrials.gov here.

Acute myeloid leukemia

Acute myeloid leukemia (relapsed and refractory)
AML is an aggressive cancer that begins as abnormal blood cells in the bone marrow, and can spread throughout the circulatory system and beyond. Almost 20,000 people in the U.S. are diagnosed with AML each year. Long-term survival with AML is poor and treatment approaches have remained largely unchanged for decades.

What is being tested?
The trial pairs an investigational drug, talazoparib, with decitabine, an epigenetic drug that is already approved for use in myelodysplastic syndrome, a disease that often precedes AML. Preclinical studies show the combining the drugs may maximize their ability to kill cancer cells.

Trial Details
Trial name: Decitabine and talazoparib in untreated AML and R/R AML
ClinicalTrials.gov number: NCT02878785
Status: Currently recruiting
Trial locations:

  • University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland
  • Other sites expected to open soon

For a list of inclusion and exclusion criteria and contact information for individual trial sites, please visit clinicaltrials.gov here.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)
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 current epigenetic therapy alone.

What is being tested?
This small pilot study is investigating whether a simple tweak to the standard care regimen may improve the current treatment’s ability to impede cancer cell growth and destroy cancer cells.

Trial details
Trial name: Epigenetics, vitamin C and abnormal hematopoiesis
ClinicalTrials.gov number: NCT02877277
Trial location: Rigshospitalet, University of Copenhagen, Denmark

For a list of inclusion and exclusion criteria and contact information for individual trial sites, please visit clinicaltrials.gov here.

Please note, maintaining proper nutrition is an important part of cancer therapy. Patients are urged to consult their doctors before making any change to their nutrition or vitamin regimen.

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML)

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML)
An estimated 13,000 people in the U.S. are diagnosed every year with MDS and an additional 1,100 are diagnosed with CMML. Both conditions are incurable with current drugs, and both can progress to acute myeloid leukemia (AML), a lethal blood cancer that accounts for more than 10,000 deaths every year.

What is being tested?
The trial studies the combination of an investigational epigenetic drug called guadecitabine with atezolizumab, a cancer immunotherapy medicine. Laboratory results show these drugs synergize to help the body’s immune system recognize and destroy cancer.

Trial details
Trial name: Guadecitabine and atezolizumab in treating patients with advance myelodysplastic syndrome or chronic myelomonocytic leukemia that is refractory or relapsed
ClinicalTrials.gov number: NCT02935361
Status: Recruiting (please see location specific information below)
Trial locations:

  • University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California (recruiting)
  • University of Maryland, Baltimore, Maryland (not yet recruiting)
  • Fox Chase Cancer Center, Philadelphia, Pennsylvania (not yet recruiting)

Industry partners: Astex Pharmaceuticals and Genentech, a member of the Roche Group

For a list of inclusion and exclusion criteria and contact information for individual trial sites, please visit clinicaltrials.gov here.

For more information, please visit ClinicalTrials.gov.

Publications of interest

The names of Dream Team members are bolded.

Publications

Muvarak NE, Chowdhury K, Xia L, Robert C, Choi EY, Cai Y, Bellani M, Z Y, Singh ZN, Duong VH, Rutherford T, Nagaria P, Bentzen SM, Seidman MM, Baer MR, Lapdius RG, Baylin SB, Rassool FV. In press. Enhancing the cytotoxic effects of PARP inhibitors with DNA demethylating agents–a potential therapy for cancer. Can Cell.

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

Lok BH, Gardner EE, Schneeberger VE, Ni A, Desmeules P, Rekhtman N, de Stanchina E, Teicher BA, Riaz N, Powell SN, Poirier JT, Rudin CM. In press. PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer. Clin Cancer Res.

Yamazaki J, Taby R, Jelinek J, Raynal NJ, Cesaroni M, Peirce SA, Kornblau SM, Bueso-Ramos CE, Ravandi F, Kantarjian HM, Issa JP. 2016. Hypomethylation of TET2 target genes identifies a curable subset of acute myeloid leukemia. J Natl Cancer Inst 108(2).

Issa JP, Roboz G, Rizzieri D, Jabbour E, Stock W, O’Connell C, Yee K, Tibes R, Griffiths EA, Walsh K, Daver N, Chung W, Naim S, Taverna P, Oganesian A, Hao Y, Lowder JN, Azab M, Kantarijian H. 2015. Safety and tolerability of guadecitabine (SGI-1110) in patients with myelodysplastic syndrome and acute myeloid leukemia: A multicenter, randomized dose-escalation phase 1 study. Lancet Oncol 16(9):1099–1110. 

Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, Han H, Liang G, Jones PA, Pugh TJ, O’Brien C, De Carvalho DD. 2015. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162(5):961–973.

Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarav V, Buhu S, Slamon DJ, Wolchok DJ, Pardoll DM, Beckmann WM, Zahnow CA, Mergoub T, Chan TA, Baylin SB, Strick R. 2015. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162(5):974–986.

Yamazaki J, Jelinek J, Lu Y, Cesaroni M, Madzo J, Neumann F, He R, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Kantaijian HM, Liang S, Estecio MR, Godley LA, Issa JP. 2015. TET2 mutations affect non-CpG island DNA methylation at enhancers and transcription factor-binding sites in chronic myelomonocytic leukemia. Cancer Res 75(14):2833–2843.

VARI-SU2C Epigenetics Dream Team News