Promising Molecule May Become Anti-Cancer Drug
Laiho: BMH-21 kills cancer, spares normal cells.
Several years ago, Marikki Laiho, M.D., Ph.D., and her research team were screening a host of molecules, looking for ones with potential to fight cancer. They found one that looked promising against prostate cancer, called BMH-21. “This molecule stood out by its novelty and great potency to kill cancer cells ,” says Laiho. But because the chemical makeup of this molecule was new, “exactly how it was able to exert its anticancer while sparing the normal cells was unknown.”
Over the last year, Laiho, Professor of Radiation Oncology and also of Oncology, and her team found BMH-21’s target: RNA polymerase I transcription. “This is a key transcription program that drives the production of building blocks for cellular protein synthesis,” says Laiho. “In most cancers, this is on overdrive. Yet even though the deregulation of this molecule is so common in cancer, no one has ever explored this as a potential form of therapy.”
Laiho’s team showed that when BMH-21 was used to treat cancer cell lines grown in culture or in mouse tumors, it proved “highly effective and led to suppression of cancer cell growth, by rapid and profound repression of RNA polymerase I transcription in a unique fashion.” Even though BMH-21 binds DNA, it had an anti-cancer effect without causing damage to the DNA itself, which is not something that can be said of conventional chemotherapy drugs. The team has since identified other novel structural variations of the parent molecule, which together with a recently granted patent will support the de velopment of the molecule to a clinical agent. “We believe that BMH-21 has particular relevance for the treatment of prostate cancers.” This research was published in Cancer Cell, the Journal of Medicinal Chemistry and the Oncotarget. One more article for the journal Molecular Cancer Therapeutics, is in press.
For this work, Laiho’s team was awarded the 2014 Prostate Cancer Foundation Global Challenge Award, which will allow the scientists to pursue the activity of BMH-21 in models of advanced prostate cancer. Laiho, the principal investigator, is working with co-investigators at Johns Hopkins and the University of Maryland: Angelo De Marzo, Charles Bieberich, Srinivasan Yegnasubramanian, Sarah Wheelan, and Paul Sirajuddin.