RNA Drug Kills Prostate Cancer Cells

A new experimental RNA-based drug has been found effective for killing prostate cancer cells.

Acting like a genetic Trojan horse, the drug tricks its way into prostate cancer cells and then springs into action to destroy them, leaving normal cells unharmed. Tests in mice with prostate cancer showed the drug shrank the size of their tumors by half, while the tumors in control mice who received no drug continued to grow. No side effects were observed from the treatment. The drug was developed at Duke University Medical Center (Durham, NC, USA). The study was reported in the August 2006 issue of Nature Biotechnology.

"This study represents the first step in creating an RNA-based drug for cancer,” said lead author James McNamara, Ph.D., a postdoctoral fellow in experimental surgery. "It provides a ‘proof of principle' that an entirely RNA-based drug can work with minimal side effects, and it shows it is possible to overcome many of the obstacles that have hampered the development of RNA-based drugs.”

The Duke team's aim was to produce a drug that would target only cancer cells. To do this, the researchers designed a drug that combined two RNA "modules” that work in stages. One module contains targeting RNA, which attaches to a protein, PMSA, found only on the surface of prostate cancer cells. When that module binds to a cancer cell, the cell reacts by engulfing the entire drug molecule.

Meanwhile, the second module, which contains silencing RNA, launches its effect. The silencing RNA seeks out and binds to the RNA for a specific cancer-causing protein, called PLK1, and tags it for destruction. This leads to the death of the cancer cell.

In mouse studies, the tumors in the 10 treated mice shrunk two-fold in volume, while the tumors in the 10 control animals more than tripled in size. "The animals themselves showed no signs of side effects,” noted Paloma Giangrade, Ph.D., co-leader of the study and an assistant research professor in experimental surgery at Duke. "Scientists have made numerous attempts to transform silencing RNAs into natural anticancer agents, but such development has been challenging,” she added.”



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