Using Statins to Target Cancer Therapy

MYC is an oncogene — a gene that’s known to cause certain forms of cancer, including prostate cancer. Studies of men with prostate cancer suggest that if MYC is present in a cancer, it is more likely to defy treatment. Mice that have the MYC gene develop prostate cancer. But when the MYC gene has been targeted for treatment in mice that have liver cancer, lung cancer, and lymphoma, the cancer has been cured.

Encouraged by these promising results, Phuoc Tran, M.D., Ph.D., The Phyllis and Brian L. Harvey Scholar, is hoping to target MYC in men with intermediate- to highgrade, localized prostate cancer. “In the past, MYC has proven diffi cult to target directly,” he says. But the use of statins — cholesterollowering drugs, taken by millions worldwide — may help. “Statins have unintended, yet beneficial, effects on cancer. They inhibit essential processes of cellular growth that include certain oncogenes.” Specifically, statins block regulatory genes, called Ras/ Rho, which, in turn, control MYC. “In addition, multiple lines of evidence suggest that statins may have a clinical effect on prostate cancer. Studies (including some led by scientists at Hopkins) have consistently shown a lower risk of advanced prostate cancer in men who take statins compared to other men. Also, taking statins seems to improve the likelihood of cure in men with prostate cancer who undergo surgery as well as radiation therapy. But none of these studies focused on how statins affect the MYC gene in prostate cancer.

“Our own laboratory data, with prostate cancer cells grown in a dish, suggest that MYC is the critical target for the cell-killing and radiosensitizing (making cancer cells more vulnerable to radiation) effects of high-dose statins,” says Tran. “All of this information suggests that high-dose statins work to kill prostate cancer cells with high MYC levels.” The best part is that, compared to other drugs that researchers suspect may help kill prostate cancer, statins are already FDA- approved, and have proven safe in widespread clinical use. “Lovastatin, in particular, is very low-cost,” says Tran. “However, it is important to pinpoint the men most likely to benefit from high-dose statin therapy. We hypothesize that MYC levels in prostate cancer can help us determine which patients will benefit from taking statins along with radiation. By using high-dose statin therapy only in men whose prostate cancer has high MYC levels, we hope to make surgery and radiation even better.” Tran is working in the laboratory to determine the right dose of lovastatin needed to inhibit MYC. Then, he plans to use his fi ndings as the basis of a clinical study in men with intermediate- to high-grade localized prostate cancer.

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