Geron Corporation (Nasdaq:GERN) today announced several presentations at the American Association for Cancer Research (AACR) Special Conference on The Role of Telomeres and Telomerase in Cancer Research held in Fort Worth, TX between February 27th and March 1st. The conference comprised ten scientific sessions with over fifty oral presentations. Geron scientists and collaborators presented recent data on the company’s telomerase inhibitor, imetelstat sodium (GRN163L), and highlighted the drug’s activity against cancer stem cells.
“Our telomerase inhibitor is showing anti-cancer stem cell activity in a range of preclinical models. In our Phase II trials of imetelstat starting this year we are targeting malignancies that are thought to be driven, at least in part, by cancer stem cells.”
“This AACR Special Conference underscores the importance of telomerase as a cancer target. What has emerged from recent preclinical studies is a growing body of evidence that telomerase is not only a broad cancer target, but a target for cancer stem cells,” said Stephen M. Kelsey, M.D., Geron's executive vice president and chief medical officer, oncology. “Our telomerase inhibitor is showing anti-cancer stem cell activity in a range of preclinical models. In our Phase II trials of imetelstat starting this year we are targeting malignancies that are thought to be driven, at least in part, by cancer stem cells.”
Cancer stem cells are small populations of cells within tumors believed to be responsible for initiating tumor growth, recurrence and metastasis. Cancer stem cells are capable of indefinite self-renewal, because of high telomerase activity, and can differentiate into all cells found in a particular tumor type. Cancer stem cells show resistance to standard chemotherapeutic agents that are effective against bulk tumor cells. After initial reduction of a tumor by standard treatments, the tumor may re-grow as a result of cancer stem cell proliferation and differentiation, causing relapse of the disease. Cancer stem cells are therefore important targets for novel therapies.
Keynote Presentation: Targeting Telomerase for Cancer Therapeutics
The Keynote presentation entitled: “Targeting Telomerase for Cancer Therapeutics” was delivered by Geron collaborator Prof. Jerry W. Shay at the University of Texas, Southwestern in Dallas, and centered on imetelstat. Prof. Shay presented data from his preclinical work on the anti-tumor effects of the drug in xenograft models of human cancers and its activity against cancer stem cells. The presentation included data published in Clinical Cancer Research in January demonstrating imetelstat’s in vitro and in vivo efficacy against glioblastoma stem cells and the drug’s ability to penetrate the blood-brain tumor barrier in an orthotopic xenograft model.
In Vivo and In Vitro Inhibition of Multiple Types of Cancer Stem Cells by the Novel Telomerase Inhibitor Imetelstat
Geron scientists and collaborators summarized a number of preclinical study results showing the efficacy of imetelstat against cancer stem cells from multiple tumor types. Imetelstat exhibits potent activity against cancer stem cells derived from primary patient samples and cancer cell lines from myeloma, melanoma, breast, pancreatic, pediatric glioma, neuroblastoma and glioblastoma. The data show that imetelstat inhibits in vitro cell proliferation and the growth of cancer stem cells, including their ability to form colonies. Imetelstat treatment also reduced the ability of cancer stem cells to form tumors in xenograft models.
Tumor Initiating Cells: A Subpopulation of Tumor Cells That Can Be Safely Targeted for Telomerase Inhibition
Dr. Uri Tabori and colleagues at the Arthur and Sonia Labatt Brain Tumor Research Center of the Hospital for Sick Children in Toronto, in collaboration with Geron scientists, presented data on pediatric neural tumor stem cells.
Prior work has shown that telomerase activity can predict survival in patients with pediatric neural tumors and Dr. Tabori and colleagues have demonstrated that in gliomas and neuroblastomas, telomere maintenance governs the unique tendency of these tumors to either undergo spontaneous growth arrest or to recur despite maximal resection and chemo-radiation therapies. Their work has also shown that telomerase is only active in the subpopulation of neural tumor cells with stem cell characteristics and that glioblastoma and neuroblastoma-derived cancer stem cell lines treated with imetelstat showed inhibition of telomerase, loss of replicative potential, progressive shortening of telomeres and cell senescence.