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FINDING CURES TOGETHER<sup>SM</sup>

Van Andel Research Institute-SU2C Cancer Epigenetics Dream Team: The VARI-SU2C Epigenetics Dream Team II

Leaders

Peter A. Jones, PhD, DSc

Peter A. Jones, PhD, DSc
Chief Scientific Officer, Van Andel Research Institute

Stephen B. Baylin, MD

Stephen B. Baylin, MD
Associate Director for Research Programs, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Overview

Epigenetic therapy is a newer approach to cancer therapy that involves switching key genes on or off to help destroy cancer cells. The Stand Up To Cancer Epigenetics Dream Team II represents the second stage of the Epigenetics Dream Team, with funding  provided by the Van Andel Research Institute.

Epigenetics describes biological processes that cells use to control whether genes are turned on or off without altering the DNA itself. Disruption of epigenetic mechanisms can also drive the disease. In contrast to genetic changes, epigenetic modifications are frequently reversible, hence providing opportunities for a new kind of therapy, called "epigenetic therapy." In this approach, epigenetic changes are targeted with drugs that reverse damage and return the expression of DNA back to its pre-cancerous condition.

Building on the successes of the original SU2C Epigenetics Dream Team, the new team is continuing to apply epigenetic therapies in combination with other treatments to multiple types of cancers, with an emphasis on clinical trials in three categories: immune sensitization, chemosensitization, and novel target strategies:

Immune sensitization: The team has combined epigenetic agents with immune checkpoint therapy in lung, blood, and multiple solid cancer patients.

Chemosensitization strategy: The team is testing a new epigenetic agent in chemotherapy-resistant colorectal cancer patients.

Novel targeting strategies: This category includes two projects: the acute myeloid leukemia trial using an epigenetic agent with a PARP inhibitor, and a study of combining a vitamin C supplement with epigenetic agents in blood cancer patients.

The VARI-SU2C Epigenetics Dream Team is taking these concepts to clinical trials and exploring the use of specific drugs to sensitize several types of cancer to chemotherapy or immunotherapy.  The team is focusing on cancers that are currently lacking in effective treatments.

Progress to Date:

  • Enrolled patients with advanced colorectal cancer in a clinical trial testing the epigenetic drug guadecitabine.

  • Enrolled  MDS/AML patients in the clinical trial combining an epigenetic drug with vitamin C. The team has observed that a single 500 mg Vitamin C tablet given daily was sufficient to restore normal vitamin C blood levels in the patients.

  • Enrolled  patients with AML in a phase I clinical trial where the safety of combining an epigenetic drug and a PARP inhibitor, is being tested. Extended survival has been observed in some patients.

  • Continued clinical trials in lung cancer and MDS.


Amount Of Funding:

$7.5 million

Principals

Anthony El-Khoueiry, MD, University of Southern California Norris Comprehensive Cancer Center

Kirsten Grønbaek, MD, DMSc, University of Copenhagen

Jean-Pierre Issa, MD, Fox Chase Cancer Center

Patricia Kropf, MD, Fox Chase Cancer Center

Charles Rudin, MD, PhD, Memorial Sloan Kettering Cancer Center