Panzem (2-methoxyestradiol ) drug a possible candidate for breast cancer treatment

Nov 2 2007

A Mayo Clinic study of a drug that has shown promise in treating sarcoma, lung and brain cancers, demonstrates that the drug may also be effective in treating breast cancer, in particular the spread of breast cancer.

The study, which was done in mouse models, is featured on the cover of the November issue of Cancer Research.

The National Cancer Institute reports that of 240,510 breast cancer diagnoses each year, about 178,480 of those women will have invasive cancer that has spread. In breast cancer, the cancer commonly lodges in the bone, destroying it in a debilitating and painful process called osteolysis. Osteolysis can lead to bone fractures that release excess calcium into the blood causing patients to feel tired or even lose consciousness.

2-methoxyestradiol (meth-oxy-es-tra-di-ol), or 2ME2, (trade name Panzem), is currently in clinical trials by other researchers as a treatment for various cancers. Mayo Clinic recently completed a clinical trial of oral 2ME2 in multiple myeloma.

2ME2 is derived from estrogen and works by suppressing tumor growth and blocking the formation of new blood vessels that feed tumors.

“2ME2 could benefit patients because this single drug essentially combines the effects of chemotherapy (which destroys cancer cells) and antiangiogenesis drugs (which destroy blood vessels that feed tumors),” states Muzaffer Cicek, Ph.D., a Mayo Clinic cell biologist in endocrine research and the corresponding author of the study.

A key part of the study is in 2ME2's ability to induce cancer cells to self-destruct, a process called apoptosis. Cells have the ability to self-destruct when damaged or infected with a virus, for example. But if a damaged cell is unable to self-destruct, it can develop into a tumor. Other studies of 2ME2 tested in other cancers, show that 2ME2 could induce cancer cells to self-destruct.

Dr. Cicek and colleagues conducted experiments in mouse models to determine whether 2ME2 would be an effective drug against breast cancer. The results are promising. Researchers described 2ME2 as an “attractive candidate for controlling tumor growth, metastasis to bone and bone disorders,” such as osteolysis caused by the spread of breast cancer to bone. Based on the study findings, the researchers propose that 2ME2 be used as a therapeutic agent to target primary tumors, metastasis to bone and tumor-induced osteolysis.

There are few effective treatments for advanced breast cancer, but in this case, the study authors feel that 2ME2 has the potential to improve the prognosis of patients with advanced breast cancer.

“Targeting metastatic tumors at sites of metastasis would be of great benefit for patients who have advanced cancer. Destroying tumors in bone and also slowing the development of osteolytic lesions would be desirable therapies and greatly improve the prognosis of patients who have bone metastasis,” the authors state.

In summary, Mayo Clinic researchers found that 2ME2 could:

• effectively target breast cancer cells
• prevent the spread of breast cancer cells to bone
• protect bone from osteolysis, which is a type of bone metastasis in which the bone is eaten away by cancer cells.

Although clinical trials of 2ME2 for breast cancer patients have not taken place, other clinical studies of 2ME2 have been conducted. These trials are based on an oral version of 2ME2 to treat primary tumors, but this method has its limitations, as the oral version of 2ME2 is poorly suited to getting into the blood system and reaching tumors. The new Mayo Clinic study resolves this by delivering 2ME2 by injection and in a lower dose -- eight times lower than the comparable oral version used in mouse models.

“We found a complete reduction of tumors in the soft tissue (mammary fat glands) and in tumors in the bone. It targeted and blocked the metastasis from soft tissue to the bone,” says Merry Jo Oursler, Ph.D., a Mayo Clinic cell biologist in endocrine research and the senior author of the study.

The researchers caution that although the study's findings are promising, they need to be replicated and tested in clinical trials.

“Our data support the conclusion that 2ME2 could be an important new therapy in the arsenal to fight metastatic breast cancer,” the researchers write.

The study is funded by a grant from the National Institutes of Health and the Mayo Clinic.

The study's authors also include: Urszula Iwaniec, Ph.D., and Russell Turner, Ph.D., of Oregon State University; Michael Goblirsch and Denis Clohisy, of the University of University of Minnesota Cancer Center; and Anne Vrabel and Ming Ruan, of Mayo Clinic.