A Silver Bullet Against Prostate Cancer

There are many weapons in our arsenal in the war on prostate cancer, and we will use many of them at the same time. For example, radiation is highly effective – it's the first line of attack against all but the most advanced forms of the disease. But some cases of the cancer become resistant to the radiation over time. In these cases, the radiation will be bolstered with drugs or some other treatment.

That's not an ideal scenario, so a team of oncologists from Johns Hopkins University set out to discover a way to beat down prostate cancer's radiation resistance, and so extend the value of radiation without having to amp up the strength of the treatment (and so risk collateral damage in the surrounding tissue).

They were fabulously successful.

The scientists discovered that a protein called DDX3 appears to be "dysregulated" in many cancers, including breast, lung, colorectal, sarcoma and prostate. The team found that the more aggressive the cancer, the higher the expression of this protein, which helps maintain cellular stability.

They had found their target. Now they needed to forge the silver bullet.

That came in the form of molecule they created that was designed to disrupt DDX3's function by locking on to a portion of the protein. The scientists showed in previous studies with cell cultures that when adding the molecule – which they call RK-33 – to malignant lung and other cancerous cells that highly express DDX3, proliferation slowed or halted, and the cells' ability to form colonies was impaired. Not only that, RK-33 appeared to be a “radiosensitizer,” making the destructive effects of radiation more pronounced. It attacked the cancer, while simultaneously draining its defenses against radiation therapy!

As expected, when researchers combined the drug with radiation, the effects were synergistic. From two to four times more cancer were killed with the tandem act than from radiation alone.

Next, the scientists tested the effects of RK-33 and radiation in mice that had been injected with human prostate cancer cells that highly express DDX3. The animals formed tumors within a few weeks, but the dual-mode treatment produced cell-killing results that paralleled their experiments in cell cultures. Better still, the experimental drug appeared to have no toxicity in the mice, suggesting that it could be a promising drug to test in humans.

"A lot of work still needs to be done to develop this into a chemotherapy drug," cautioned Venu Raman, PhD, an associate professor of radiology and radiological science and of oncology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center. "But based on our findings, we think it could fill an un-met need in making the most common treatment for prostate cancer more effective."

The data have been published in Cancer Research.