UI testing drug that shows promise against some cancers

UI testing drug that shows promise against some cancers

CHAMPAIGN — University of Illinois researchers are testing a new drug that is showing promise for patients with certain types of breast, ovarian and endometrial cancers.

The drug is called BHPI, for short, and it could eventually be used to treat cancers classified as estrogen receptor-positive — meaning cancers containing cell proteins that are activated by the hormone estrogen.

BHPI was tested in mice injected with human breast cancer, and it quickly halted the growth of most of the tumors and caused them to shrink, according to UI biochemistry Professor David Shapiro, the senior author of the newly published research.

Within 10 days, the drug stopped cancer growth in 48 out of 52 tumors and caused most of them to shrink by 30 to 50 percent, he said.

"Most cancer drugs work by inhibiting something the cancer cells need," Shapiro said. "Our drug takes something that cancer cells use to protect themselves and overactivates it, makes them burn up their energy and kill themselves."

Cellular tests have also shown the drug had a similar effect stopping estrogen-positive endometrial and ovarian cancers, he said. Tests on mice with those types of tumors will be the next step.

About 70 percent of breast cancers contain estrogen receptors, Shapiro said.

In many cases, surgery effectively removes the tumors and current therapies keep the cancers from reappearing, he said. But still, about half of breast cancer deaths are the result of estrogen receptor-positive tumors.

A major reason for that is the drugs commonly used to treat and prevent recurrences of estrogen receptor-positive cancers — tamoxifen and aromatase inhibitors — become ineffective over time, Shapiro said.

Tamoxifen works by blocking estrogen receptors in breast cancer cells, and aromatase inhibitors lower estrogen levels.

A feature that has made tamoxifen attractive as a treatment has been the fact that it isn't toxic, so it doesn't produce the severe symptoms many other drugs do, "and initially, it's quite effective," Shapiro said.

But in patients with estrogen reactor-positive breast cancer that has metastasized, or spread, the tumors will eventually resume growing, he said.

How BHPI works differently than treatments currently available: It works by hijacking a pathway that the cancer cells normally use for protection and uses it to kill them, Shapiro said.

"So what it does is it hyperactivates this pathway and this converts the pathway from becoming protective to lethal," he said. "Because this pathway is already elevated in cancer resistant to current therapies, our drug actually works better in cancer cells that are resistant to current therapies."

And, importantly, Shapiro adds, the cancer cells don't just stop growing.

"They die," he said.

Another reason to be optimistic: Shapiro said the amounts of the drug compound that have been given to mice have been "quite low" doses at realistic levels.

Cellular testing done so far with BHPI on the often deadly ovarian cancer — which is estrogen receptor-positive in one-third to half of all cases — has also shown the drug to be highly effective, Shapiro said, "but we still have a lot more work to do."

Depending on future test results and research funding, the drug could be in clinical trials within a few years, he said.

BHPI has a series of increasingly difficult hurdles to surmount, Shapiro said, and "one reason we are so enthusiastic is it's been clearing the hurdles by a wide margin."

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