In a study described in the January 13 issue of Cancer-Cell, Marikki Laiho, M.D., Ph.D., and her colleagues say their work focused on the ability of a chemical dubbed BMH-21 to sabotage the transcription pathway RNA Polymerase pathway (POL I), shutting down the ability of mutant cancer genes to communicate with cells and replicate.
Laiho's research linked the pathway to p53 gene activity. P53 is a tumor suppressor gene, a protein that regulates cell growth, and it is the most frequently mutated suppressor gene in cancer.
Transcription pathways are the means by which certain proteins that direct cell division are 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.
"Without this transcription machinery, cancer cells cannot function," says Marikki Laiho, M.D., Ph.D., professor of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins and senior author on the study.
Laiho said BMH-21 was identified using by screening a library of chemical compounds known to have potential for anticancer activity based on their chemical structure and capabilities. Specifically, they looked for the ability of those compounds to interfere with transcription in human tumor cells obtained through the National Cancer Institute's collection of 60 human tumor cell lines of nine different cancer types, including melanoma and colon cancer.
BMH-21 first jumped out, Laiho said, demonstrating potent action against melanoma and colon cancer cells. In fact, in these studies, the drug functioned better in upsetting these cancer cells' activities than many FDA-approved cancer drugs.
BMH-21 also appears to overcome the tendency of cancer cells to resist chemotherapeutic agents because it finds and targets proteins and shuts down the communication pathways that cells use to continue dividing.
"One of the challenges of current cancer therapies, including new targeted therapies, is a cancer cell's ability to overcome a treatment's anticancer properties. The characteristics of a cancer cell and its circuitry is very complex and results in many changes and mutations that allow the cells to continue to thrive despite cancer treatments," said Laiho.
While the findings with BMH-21 are promising, Laiho cautions much more study of the compound is needed before it would be ready for studies in patients. She and her team are continuing studies of the drug in animal models to further reveal the drug's potential against cancer and 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.
Laiho is currently collaborating with Kimmel Cancer Center drug development experts as well as multiple myeloma blood cancer, medullary thyroid cancer, and prostate cancer experts to further explore the drug's cancer-fighting abilities. She also is collaborating with investigators at a laboratory in Helsinki, Finland, where she maintains an affiliation.
In addition to Laiho, other members of the research team include Karita Peltonen, Laureen Colis, Hester Liu, Rishi Trivedi, Michael S. Moubarek, Henna M. Moore, Bayoan Bai, Michelle Rudek, and Charles J. Bieberich.
The research was supported by the Academy of Finland, Biomedicum Helsinki Foundation, Cancer Society Finland, Finnish Cultural Foundation, Patrick C. Walsh Cancer Research Fund, the National Institutes of Health, Johns Hopkins University start-up funds, and the Analytical Pharmacology Core of the Johns Hopkins Kimmel Cancer Center.
Amy Mone | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News