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KDM1 May Represent a New Therapeutic Target for Glioma

April 7, 2013
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  • The protein KDM1 was overexpressed in gliomas.
  • KDM1 inhibition reduced glioma cell proliferation in vitro.
  • KDM1 inhibition reduced glioma growth in a mouse model.

WASHINGTON, D.C. — Researchers have generated preclinical data demonstrating that the protein KDM1, which functions as a lysine demethylase, is a potential target for glioma treatment, according to Gangadhara R. Sareddy, Ph.D., a postdoctoral fellow in the Vadlamudi Laboratory at The University of Texas Health Science Center in San Antonio, who presented the results at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“We found that KDM1 expression is upregulated in gliomas and have preclinical evidence that suggests pharmaceutical inhibition of the KDM1 axis could have therapeutic implications for the treatment of gliomas,” said Sareddy.

Gliomas, the deadliest form of primary central nervous system neoplasms, represent about 70 percent of brain tumors, according to Sareddy. Roughly 20,000 patients are diagnosed with gliomas each year in the United States.

“Patients with malignant gliomas have a survival time of approximately 14 months,” Sareddy said. “Novel therapies are urgently needed. Evolving evidence suggests that glioma development is a multistep process that results from changes both in genetic and epigenetic mechanisms. Unlike genetic alterations, epigenetic changes are reversible; therefore, targeting epigenetic changes represents a promising therapeutic approach.”

He and his colleagues set out to assess the importance of KDM1 in gliomas. Through immunohistochemical analysis, they found that KDM1 expression was elevated in gliomas. They silenced KDM1 expression with siRNA or inhibited it with pargyline or NCL-1 and found that reducing its expression or inhibiting it pharmacologically reduced glioma cell line growth in vitro. In addition, inhibiting KDM1 pharmacologically reduced the growth of patient-derived primary glioblastoma multiforme cells in vitro and the growth of a human glioma cell line in mice.

Results of mechanistic studies demonstrated that inhibiting KDM1 increased the expression of tumor suppressor p53 target genes through epigenetic modifications, according to Sareddy.

“Because KDM1 plays a critical role in glioma biology and because epigenetic modifications are reversible, pharmacological inhibition of KDM1 could be a potential therapy for gliomas,” Sareddy said. “Identification of KDM1 as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in patients with glioma.”

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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

Media Contact:
Jeremy Moore
(215) 446-7109
Jeremy.Moore@aacr.org
In Washington, D.C.,
April 6-10, 2013:

(202) 249-4005

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