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Promise and Progress - Shutting Down Cancer Cells

Reprogramming Cancer Cells - The Story of Epigenetics
Issue No. 1

Shutting Down Cancer Cells

Date: July 16, 2014

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In studies using human cancer cell lines directed by researcher Marikki Laiho, a new, never described compound destroyed a critical communication pathway that mutant cancer genes use to communicate with cancer cells.

Researchers have uncovered a potential way to stop cancer cells in their tracks.  The studies are in a very early stage, but they have demonstrated the ability in laboratory and animal studies to completely shut down the cellular machinery cancers need to survive.

The research focuses on the RNA polymerase pathway, POL I, which is necessary for mutant cancer genes to communicate with cells.  In studies using human cancer cell lines, directed by Marikki Laiho, M.D., Ph.D., the Willard and Lillian Hackerman Professor of Oncology and Director of Molecular Radiation Sciences, a new, never-described compound known as BMH-21 destroyed this critical communication pathway.  “Without this transcription machinery, cancer cells cannot recover,” says Dr. Laiho.  “The cancer cells cannot function.”

POL I is known as a transcription pathway. It is how proteins, which direct cell division, are translated and put into action by cells.  Uncontrolled cell division is a hallmark of cancer, and BMH-21 has demonstrated an ability to bind to the DNA of cancer cells and completely shut down this transcription pathway. 

Preliminary studies were completed using human tumor cells obtained through the NCI60 platform, a collection of 60 human tumor cell lines of nine different cancer types.  Dr. Laiho and team collaborated with experts from the National Cancer Institute’s Developmental Therapeutics Program to screen a library of compounds for potential anticancer activity.  BMH-21 jumped out, demonstrating potent action against melanoma cancer cells.  In fact, in these studies, the drug functioned better against the cancer cells than many FDA-approved cancer drugs.

While the findings are promising, Dr. Laiho cautions much more research of this new compound is needed before it would be ready for studies in patients.   She and her team will continue to examine the drug in animal models to further reveal its potential against cancer and its possible toxicities and to determine dosage.  The transcription machinery the compound shuts down is common among all cancer cell types, so the researchers believe it has therapeutic potential across many tumor types.  Dr. Laiho is currently collaborating with Kimmel Cancer Center drug development experts and multiple myeloma blood cancer, medullary thyroid cancer, and prostate cancer experts to further explore the drug’s cancer-fighting abilities.  She is also is collaborating with investigators at a laboratory in Helsinki, Finland, where she maintains an affiliation.

The research was supported by the Academy of Finland, Biomedicum Helsinki Foundation, the Cancer Society of Finland, the Finnish Cultural Foundation, the Patrick C. Walsh Prostate Cancer Research Fund, the National Institutes of Health, Johns Hopkins University start-up funds, and the Pharmacology Analytical Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

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