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The Leukemia & Lymphoma Society Announces Recipients of The Screen to Lead Grant Program

Five Distinguished Researchers Receive First-Time Grant

WHITE PLAINS, N.Y., Jan. 16, 2014 /PRNewswire/ -- The Leukemia & Lymphoma Society (LLS) today is pleased to announce the researchers who will receive funding through The Screen to Lead program - a new grant program to support drug discovery specifically directed toward medicinal chemistry and/or drug target screening in blood cancers.  

LLS recognizes investigators' significant need for resources to develop small molecules into drug-like compounds suitable for preclinical proof-of-concept testing in cancer models.  The goal is to fill a gap in the drug development process in academic laboratories, with the potential that novel targeted therapies may eventually be evaluated and benefit patients.

"LLS funds research to advance more breakthrough therapies for cancer patients.  This funding support is specifically designed to advance promising compounds in the earliest stages of development," said Lee Greenberger, Ph.D., LLS chief scientific officer.  "It is critically important that leading scientists and researchers get financial resources to pursue innovative, novel approaches that can change the standard of care for patients with blood cancers."

The amounts of the grants awarded to these innovative researchers will vary and be determined on a case by case basis. The awardees are:

Li Chai, M.D. – Brigham and Women's, Boston
Chai will target SALL4 in the treatment of acute myeloid leukemia (AML).  SALL4 is a transcription factor – a protein that regulates genetic activity, and is abnormally expressed in most AML patient samples.  Chai's team has been testing a peptide that can block SALL4.  While peptides can be useful as tools, they have low stability in the body so the team is performing high throughput tests to identify other compounds with drug-like characteristics that might also be effective in blocking SALL4. The team has produced an assay, a laboratory test that enables researchers to examine thousands of compounds, that will be used by a contract research organization (CRO) to identify those that are effective against SALL4.

Michael Deininger, M.D., Ph.D. – Huntsman Cancer Institute, Salt Lake City
Signal Transducer and Activator of Transcription 3 (STAT3) is a protein involved in the regulation of cell growth and survival.  It is frequently super-activated in patients with certain cancers.  Deininger has developed assays to identify STAT3 inhibitors and through medicinal chemistry approaches, has generated more potent inhibitors.  The grant will assist him in his goal of making compounds more effective at inhibiting STAT3 at lower doses.  Promising compounds will be synthesized on a larger scale and will be tested in animal models of therapy-resistant chronic myeloid leukemia (CML) as well as in myelofibrosis (MF).  Since STAT3 is activated in a number of cancers, compounds developed may be useful beyond CML and MF.

Yali Dou, Ph.D. – University of Michigan
Epigenetics are small chemical modifications that alter gene activity without changing the DNA code of those genes.  Abnormal epigenetic changes are often associated with the growth of cancer cells.  A protein known as mixed-lineage leukemia protein (MLL) works with a host of other proteins to mediate such epigenetic alterations and is genetically altered in certain patients with AML resulting in a particularly poor prognosis for these patients.  Dou's team has developed an assay whereby purified MLL and its associated co-regulator proteins are mixed, and their epigenetic modifying activity can be quantitatively measured.  They will screen large libraries of compounds with drug-like characteristics in this assay, and determine which ones can inhibit the epigenetic modifying activity.  Positive hits in the screen will be used as lead compounds for improvement, which can then be tested in cancer models as antitumor agents.

Aaron Schimmer, M.D., Ph.D. – Princess Margaret Cancer Center/Ontario Cancer Institute
The proteasome is a machine in the cell that regulates the degradation of proteins in the cells, and is essential to getting rid of proteins no longer needed.  In addition, the proteasome is crucial to the normal cell signaling process required for growth and survival of the cell.  Certain cancer cells, such as those found in patients with multiple myeloma, have high levels of proteasome activity.  Thus, inhibiting the proteasome has been an effective anti-cancer therapy, as is the case of Velcade® in patients with multiple myeloma.  Velcade targets the proteasome in the cytoplasm.  Schimmer has recently shown that inhibiting the proteasome in the mitochondria (energy factory) has anti-tumor activity.  This is a novel approach to cancer therapy, and the identification of a drug specifically targeting the mitochondrial proteasome may lead to a first-in-class drug for treatment of patients with AML and potentially other cancers.

David Williams, M.D. – Children's Hospital Boston
The Rac proteins are required for cancer development in a number of systems.  Williams has explored the role of these proteins in CML, AML, and more recently, acute lymphocytic leukemia (ALL).  His team has shown that inhibition of Rac can lead to cancer cell death.  From previously LLS-funded research, compounds were identified that inhibit Rac and were tested as anti-cancer agents.  They successfully identified a number of lead compounds worthy of further refinement.  The purpose of this grant is to continue the project to use a medicinal chemistry approach to improve these compounds, potentially identifying lead compounds that may be candidates for clinical evaluation. 

About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society ® (LLS) is the world's largest voluntary health agency dedicated to blood cancer. The LLS mission: Cure leukemia, lymphoma, multiple myeloma, and improve the quality of life of patients and their families. LLS funds lifesaving blood cancer research around the world, provides free information and support services, and is the voice for all blood cancer patients seeking access to quality, affordable, coordinated care.  

Founded in 1949 and headquartered in White Plains, NY, LLS has chapters throughout the United States and Canada. To learn more, visit www.LLS.org. Patients should contact the Information Resource Center at (800) 955-4572, Monday through Friday, 9 a.m. to 6 p.m. ET.

Contact: Andrea Greif
(914) 821-8958
andrea.greif@lls.org

SOURCE The Leukemia & Lymphoma Society

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