Mighty Mouse Fights Cancer

by Jeff Worley
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A mouse resistant to cancer, even very aggressive types, has been created by researchers at the University of Kentucky. The breakthrough stems from a discovery by UK professor of radiation medicine Vivek Rangnekar and a team of researchers who found a tumor-suppressor gene called Par-4 in the prostate. The researchers discovered that this gene performs the slickest trick an anti-cancer agent can: it kills cancer cells, but not normal cells. 

Funded by several grants from the NIH, Rangnekar’s study is unique in that mice born with this gene don’t develop tumors. The mice grow normally and have no defects. In fact, the mice possessing Par-4 actually live a few months longer than lab mice without the gene, indicating that Par-4 mice have no toxic side effects.

“We originally discovered Par-4 in the prostate, but it’s not limited to the prostate. The gene is expressed in every cell type that we’ve looked at, and we’ve seen that it induces the death of a broad range of cancer cells, including, of course, cancer cells in the prostate,” says Rangnekar. “The interesting part of this study is that this killer gene singles out cancer cells. It will not kill normal cells, and there are very few selective molecules out there like this.”

To further investigate the potential therapeutic benefits of this selective assassin, Rangnekar’s team put it into the egg of a mouse. That egg was then implanted into a surrogate mother. “The mouse itself does not express a large number of copies of this gene, but the pups do and then their pups start expressing the gene,” says Rangnekar exuberantly. “So we’ve been able to transfer this activity to generations in the mouse.”

To further establish the power of Par-4, his group removed the gene from several mice. The result: tumors developed in various tissues of the animal.

Rangnekar speculates that this gene may one day be transplanted into a patient’s bone marrow to fight cancerous cells in the body. This process could be combined with chemotherapy and radiation, which on their own have highly toxic effects on healthy cells, in order to lower toxicity. But Rangnekar admits there is much more work to be done before this research can be applied to people.

“I look at this research from the standpoint of how it can be developed to benefit the cancer patient, and that’s what keeps us focused,” says Rangnekar. “The pain that cancer patients go through—not just from the disease, but also from the treatment—is excruciating. If you can treat the cancer and not harm the patient, that’s a major breakthrough. That’s happening with these animals, and I think it’s wonderful.”

The research was published in the journal Cancer Research. Rangnekar holds the Alfred Cohen, M.D., Endowed Chair in Oncology Research and serves as the associate director for translational research at the UK Markey Cancer Center.