Meet BMH-21. This little studied molecule has been hiding in a library of potential anticancer agents, successfully evading the pipettes and petri dishes of cancer researchers.
However, thanks to a study published by Johns Hopkins University researchers in the January 2014 issue of Cancer-Cell, this low-key identity is about to change. According to the study, BMH-21 can stop the uncontrollable division of cancer cells, thereby impeding a tumor’s ability to grow and spread throughout the body.
BMH-21 disrupts cancer cell division by acting on the RNA Polymerase (POL 1) pathway. Normally, this pathway allows cells to transcribe DNA. This initiates the process by which genetic information is converted to a form that can be understood and utilized by the host cell.
While this process is vital to all cells, mutated genes can hijack it, prompting the cellular communication that leads to unnecessary DNA replication. This duplication process invariably leads to uncontrolled cell division, the hallmark of cancer. Thus, by disrupting the POL 1 pathway, BMH-21 can impede a cancer cell’s ability to replicate and can therefore stop tumor cell growth.
The team of researchers that conducted the study found BMH-21 through a screen of compounds thought to have anticancer activity. These compounds, first identified as potential anticancer agents through their chemical structures and cellular capabilities, were tested for biological activity on the National Cancer Institute’s collection of 60 human tumor cell lines.
BMH-21 arose as a distinct compound of interest, as it worked better than some FDA approved drugs on melanoma and colon cancers.
On the lab-grown human tumor cell lines, BMH-21 appears to alter the POL 1 transcription pathway through the activity of p53. This links the newly identified anticancer agent to a well-researched tumor suppressor gene. In normal cells, p53 transcription suppresses cellular division, preventing any unchecked growth. However, p53 is known to be mutated in many cancer cells, rendering it incapable of working against the cancerous proliferation of cells. Thus, if it truly acts through p53, BMH-21 may help cells regain the p53 tumor suppressor function, stopping uncontrolled cell division in its tracks.
Despite this compound’s promise as an anticancer agent, more research needs to be conducted before BMH-21 can be used in patients. Marikki Laiho, a physician and professor of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins University and senior author of this study is leading her team to continue studies of BMH-21 in animals. This will help find toxicities and determine proper dosages. Furthermore, because BMH-21 hits a process common to all cancer types, these studies may help identify the forms of cancer that best respond to BMH-21 therapy.
While conducting this study, Laiho’s team collaborated with Kimmel Cancer Center drug development experts and scientists studying multiple myeloma blood cancer, medullary thyroid cancer, and prostate cancer. The team also had significant contact with researchers in Helsinki, Finland. The research was supported by a combination of American and Finish organizations: 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.
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