BMH-21 demonstrates potential in shutting down common cancer process
A previously known but little-studied chemical compound targets and shuts down a common cancer process, according to recent research. In studies of laboratory-grown human tumor cell lines, the drug disrupted tumor cell division and prevented growth of advanced cancer cells.
In a study described in Cancer Cell (2014;25:77-90), senior author Marikki Laiho, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues 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 that is translated into 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," said Laiho.
Laiho said BMH-21 was identified by screening a library of chemical compounds known to have the 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 explained, and demonstrated 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.
Although the findings with BMH-21 are promising, Laiho cautions that 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.