Cell Death In Leukemia Induced By Massey Researchers

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Biology / Biochemistry
Article Date: 21 Apr 2007 - 5:00 PDT

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Researchers from the Virginia Commonwealth University Massey Cancer Center have presented preclinical research at the American Association of Cancer Research's annual meeting suggesting the potential of a new combination treatment for chronic lymphocytic leukemia (CLL).

In this study, led by Steven Grant, M.D., Massey's associate director of translational research, interactions between bortezomib and romidepsin (Gloucester Pharmaceuticals) and bortezomib with belinostat (aka PXD101 from CuraGen Corporation and TopoTarget A/S), were examined in human CLL cells isolated from five patients. Bortezomib dramatically potentiated the lethality of both agents in cells from four of five patients, while exerting additive effects in cells from one patient. Notably, pronounced lethality was observed following treatment of cells with very low concentrations of the agents.

Parallel studies conducted on two established CLL cell lines provided additional preclinical evidence that bortezomib interacts synergistically with both agents to induce cell death in human CLL cells. Romidepsin and belinostat are histone deacetylase (HDAC) inhibitors.

"To the best of our knowledge, this is the first report describing synergistic interactions between HDAC inhibitors and Bortezomib combinations in the setting of CLL," said Grant. "The findings of our study -- as well as the emerging body of preclinical and early clinical data suggesting interactions between HDAC inhibitors and bortezomib in other tumor cell types, particularly hematologic malignancies -- is certainly of interest and warrants further investigation as a potential therapeutic strategy in CLL."

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About the VCU Massey Cancer Center: The VCU Massey Cancer Center is one of 61 National Cancer Institute-designated institutions that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers more clinical trials than any other institution in Virginia, serving patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at http://www.massey.vcu.edu/.

About Romidepsin and Gloucester Pharmaceuticals, Inc.: Romidepsin is a novel agent in a new class of anti-cancer drugs known as histone deacetylase inhibitors. Gloucester Pharmaceuticals is conducting a pivotal phase II study of romidepsin for patients with cutaneous T-cell lymphoma (CTCL) and has initiated a pivotal phase II study for patients with peripheral T-cell lymphoma (PTCL). Romidepsin has received Orphan Drug Designation from the Food and Drug Administration (FDA) for the treatment of non-Hodgkin T-cell lymphomas, which includes CTCL and PTCL. In addition, the European Agency for the Evaluation of Medicinal Products (EMEA) has issued Orphan Drug status for the treatment of both CTCL and PTCL. Fast Track status for CTCL has also been designated by the FDA. Romidepsin is in clinical trials for a variety of other hematological malignancies and solid tumors, including hormone refractory prostate cancer, pancreatic cancer and multiple myeloma. These trials and others are being conducted by the Company or the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) with the Company.

Gloucester Pharmaceuticals, Inc. is a privately held, venture-backed company that develops and commercializes innovative products for the treatment of cancer patients. Gloucester is headquartered in Cambridge, MA. For more information on Gloucester and its clinical development program, visit http://www.gloucesterpharma.com/.

About belinostat, CuraGen Corporation and TopoTarget A/S: Belinostat is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents. Intravenous belinostat is currently being evaluated in multiple mid-stage clinical trials as a potential treatment for multiple myeloma, T- and B-cell lymphomas, AML, mesothelioma, liver, colorectal, and ovarian cancers, either alone or in combination with anti-cancer therapies. An oral formulation of belinostat is also being evaluated in a Phase I study for patients with advanced solid tumors. Under a Clinical Trials Agreement signed with CuraGen, the NCI is sponsoring several clinical trials investigating belinostat for the treatment of various cancers, both as a single-agent and in combination chemotherapy regimens. In order to better understand belinostat's anti-tumor activity and to provide supporting information for clinical trials, TopoTarget signed a Cooperative Research and Development Agreement (CRADA) with the NCI to conduct preclinical and nonclinical studies with belinostat.

CuraGen Corporation (Nasdaq: CRGN) is a biopharmaceutical company developing diverse approaches, including novel protein, antibody, antibody- drug conjugate and small molecule therapeutics to address the unmet medical needs of patients with cancer and inflammatory diseases. CuraGen Corporation is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com/.

TopoTarget (CSE: TOPO) is a biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK and Germany, dedicated to finding "Answers for Cancer" and developing improved cancer therapies. TopoTarget has a broad portfolio of small molecule preclinical drug candidates and seven drugs are in clinical development, including both novel anti-cancer therapeutics and new cancer indications for existing drugs. For more information, please refer to http://www.topotarget.com/.

Contact: Andrea Butler
Virginia Commonwealth University

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