MU researcher discovers drug may reduce breast cancer tumors

Wednesday, February 18, 2009 | 7:56 p.m. CST
Salman Hyder researches tumors with accelerated growth and a non-toxic alternative to chemotherapy for treating breast cancer.

COLUMBIA — An MU researcher says he has found that a certain drug could possibly be a non-toxic alternative to chemotherapy for treating breast cancer.

Salman Hyder, the Zalk Missouri Professor of Tumor Angiogenesis in the department of biomedical sciences, discovered that a drug called PRIMA-1 is effective at modifying a certain protein to help suppress cancerous tumors from forming. According to Hyder, the drug, which is in pre-clinical stages, could be effective for treating a large number of women since most breast tumors contain abnormal protein.

The research focuses on tumors that have accelerated growth because of use of progestin, a hormone commonly used in birth control pills and Hormone Replacement Therapy (HRT) for women in menopause.

“The clinical trials in humans have shown that women who are consuming estrogens and progestins are at increased risk of breast cancer. They are developing tumors, and they are developing tumors very fast after they start taking this, like within two or three years,” Hyder said. “That means progestin is driving these tumors. So clearly, progestin has an effect on tumor development.”

Even though progestin has been linked to causing breast cancer, it is still included in HRT because it decreases the risk for uterine cancer.

PRIMA-1, the drug used in the study, is able to target abnormal p53, the protein most responsible for breast cancer. Some cases of breast cancer, which will affect one out of every eight women during their lifetimes, occur because of a mutation in p53. When the protein is normal, it suppresses tumors; when it is mutated, it can't. PRIMA-1 is able to reverse the mutation and make normal p53.

“What it’s doing is working on a cellular level to help restore or turn on a gene that was turned off,” said Paul Dale, chief of surgical oncology at Ellis Fischel Cancer Center. “If we could turn it back on again, then it’s the body’s way of fighting cancer.”

Dennis Lubahn, a professor of biochemistry at MU, is familiar with Hyder's research and described it as very promising.

“Usually these p53s are bad news, but if you have something that can target them, it is as slick as all-get-out,” he said.

In his experiments with rats, Hyder and co-workers have found PRIMA-1 to be extremely effective. Scientists could treat 40 to 50 percent of the tumors in the rats, and the rest of the tumors slowed down or became stable.

“In cancer research, anything up to 10 percent and beyond is huge in terms of treatment,” Hyder said.

Although it has not undergone clinical trials yet for this particular use, scientists speculate PRIMA-1 could one day be an alternative to chemotherapy for many breast cancer patients.

Hyder noted that chemotherapy can be very toxic. So far, PRIMA-1 seems to be non-toxic.

“The drug really works. When we give it to animals, there is no toxicity to the animals and no suffering for the animals after we give them this drug,” he said. “The idea would be hopefully that if it’s given to women that they would be able to tolerate it.”

Lubahn said it is this quality that makes PRIMA-1 "amazing."

“It’s almost like a magic bullet in some ways because there doesn’t seem to be much toxicity in it,” Lubahn said.

Hyder said PRIMA-1 could also be given to women prone to progestin-accelerated tumors to prevent or delay the growth of tumors.

“Potentially it could protect tumors coming up and women who already have taken (progestin and estrogen) and are prone to tumors and if they are given PRIMA, maybe you can protect them from the emergence of tumors,” he said. “But until clinical trials are done, we will never know.”

Hyder also said it is unclear at present if PRIMA-1 could stop tumors from forming at all.

“It is preventative in a sense, but not from the beginning because we have not tested it,” he said.

Hyder hopes to conduct research on that possibility, but the costly experiments will require additional funding. His current funding comes from the National Institutes of Health, the U.S. Department of Defense Breast Cancer Program and the Susan G. Komen Breast Cancer Foundation.

Still, Hyder said, "We are going to try and get some and do this because this is kind of exciting.”

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