The compound — which they call metarrestin — destroys a unique structure inside the nucleus of cancer cells that can spread and form new tumors.
A paper on the work — in which researchers from the National Institutes of Health (NIH) collaborated with those from Northwestern University Feinberg School of Medicine in Chicago, IL — is published in Science Translational Medicine.
In describing how metarrestin works, co-corresponding study author Sui Huang, who works as an associate professor of cell and molecular biology at Northwestern University Feinberg School of Medicine, likens it to a “dirty bomb against cancer.”
“It could potentially result in a better outcome for patients with solid tumor cancers with high potential to spread to other organs,” she adds.
Metastasis — ‘the final frontier’
Cancer would not be such a potentially serious disease if it were not capable of metastasis, which is a complex process wherein cancer cells escape the primary tumor and invade nearby or distant tissue to form new, secondary tumors.
“What kills people,” Prof. Huang explains, “is when cancer spreads to other organs, such as when breast cancer spreads to the brain, liver, lungs, or bones.”
Metastasis is sometimes referred to as “the last frontier of cancer research.” It accounts for around 90 percent of cancer deaths and this figure has not altered much in half a century.
Once a cancer reaches the metastatic stage, it becomes very difficult to treat with current methods, which are much more effective at tackling the primary tumor.
“Many drugs,” explains co-corresponding study author Dr. Juan Jose Marugan, group leader of the Chemical Genomics Center at the NIH’s National Center for Advancing Translational Sciences in Rockville, MD, “are aimed at stopping cancer growth and killing cancer cells.”
But so far, no drug has been approved that is designed specifically against metastasis, he adds.
Metarrestin kills perinucleolar compartments
Metarrestin destroys a little-understood structure inside the nucleus of cancer cells that is known as the “perinucleolar compartment (PNC).”
Tests on laboratory-cultured cancer cells and cells sampled from human tumors have shown that “PNCs selectively form in cells from solid tumors.”
Also, in previous work, Prof. Huang and her team had discovered that the likelihood of cancer spread was greater when tumor cells had more PNCs.
This led the team to wonder whether attacking PNCs might reduce cancer spread and improve patients’ prospects.
In this study, the scientists used “high-throughput screening followed by chemical optimization” to assess which compound, from a list of at least 140,000, might have the greatest power to destroy PNCs in metastatic cancer cells.
They whittled down the list to 100 compounds, and then they identified one that destroyed PNCs in metastatic prostate cancer cells.
A modified version of the compound became metarrestin, which “significantly inhibited metastasis” in mice grafted with human pancreatic, breast, and prostate cancer. The treated mice also lived longer than untreated mice.
The researchers intend to apply for metarrestin to enter the Food and Drug Administration (FDA) new drug investigation process later this year, after they have run more preclinical tests and collected the data required.
“Our results show metarrestin is a very promising agent that we should continue to investigate against metastasis.”
Dr. Juan Jose Marugan
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