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U-M CCC - Progress Newsletter Winter 2004 Online

Research Update


Telltale Protein Linked to Prostate Cancer Appears Crucial to Breast Cancer, too

Like a killer charged with more than one murder, a tiny protein that has already been linked to deadly prostate cancer is now being implicated in lethal breast cancer. And it may soon help doctors tell cancer patients just how dangerous their tumors are.

The protein, EZH2, appears to help cancer cells invade nearby tissue and form colonies, according to a study published in the Sept. 30, 2003 issue of the Proceedings of the National Academy of Sciences.

But like many killers who get caught, EZH2 also leaves "fingerprints" -- copies of the protein that can easily be detected in cancerous tissue. In the new study, led by scientists from the U-M Comprehensive Cancer Center, levels of EZH2 in a patient"s tumor corresponded to the tumor"s level of danger. The more EZH2 there was, the deadlier the cancer and the worse the patient"s outcome. The new results linking EZH2 to breast cancer, and describing the mechanism of its role in cancer's spread, are based on the examination of tissue samples, medical records from 280 U-M breast cancer patients, and studies in cell cultures. This exhaustive analysis was conducted by a team from U-M, the University of Amsterdam and Harvard Medical School. Members of this team previously reported EZH2's role in aggressive and metastatic prostate cancer.

"EZH2 may serve as an excellent biomarker for determining a breast cancer patient's prognosis more precisely than current methods," says lead author Celina G. Kleer, M.D., an assistant professor of pathology at the U-M Medical School. "Just as with prostate cancer, its association with the severity of a patient's disease, and clinical outcome, is striking. And it is easy to detect with an antibody stain."

The actual use of EZH2 as a clinical tool is still several years away, though the U-M team is planning a prospective clinical trial to test its use in breast cancer patients. "If our work is confirmed through carefully controlled clinical trials, testing for EZH2 would be a relatively straightforward and feasible way to judge a patient's prognosis and help determine her best course of treatment," Kleer says. "For tens of thousands of women a year, that could mean a lot."

In addition to Celina Kleer, the study's authors are: senior author Arul Chinnaiyan, M.D., Ph.D., assistant professor of pathology and urology at U-M; U-M co-lead authors Qi Cao and Sooryanarayana Varambally; U-M co-authors Ronglai Shen, Ichiro Ota, Scott A. Tomlins, Debashis Ghosh, Daniel Hayes, Michael S. Sabel, Donna Livant, and Stephen J. Weiss; Richard G. Sewalt and Arie Otte of the Swammerdam Institute for Life Sciences at the University of Amsterdam; and Mark Rubin of Brigham and Women"s Hospital, Harvard University.

Patients interested in breast cancer and prostate cancer research at the University of Michigan Comprehensive Cancer Center may call the U-M Cancer AnswerLine™ at 1-800-865-1125; or visit them on-line.

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U-M Leads National Study to Examine Couples' Quality of Life Beofre, After Prostate Cancer Diagnosis to Ease Their Fears About Treatment

Today, improved prostate cancer treatments are enabling physicians to cure most of the one in nine American men diagnosed with prostate cancer. But even with lifesaving medical care available, men still worry about how the possible side-effects of their treatment -- from sexual dysfunction to temporary incontinence and rectal problems -- will affect their overall quality of life and the intimate relationship they have with their partners.

To offer men recovering from prostate cancer a better understanding of what they may face, physicians at the University of Michigan are leading a national study funded by the National Cancer Institute to examine how prostate cancer treatments may affect a couple's intimacy and quality of life.

"Patients who have been diagnosed with prostate cancer must often make difficult choices between various surgical options, radiation therapy, radioactive seed implants or watchful waiting," explains Martin Sanda, M.D., associate director for the Prostate Cancer and Urologic Oncology Program at the U-M Comprehensive Cancer Center. "When men are diagnosed, they often are concerned or become somewhat anxious about the possible side effects of prostate cancer treatments," says Sanda. "The side effects men often fear involve their sexuality, urinary functioning or possible rectum symptoms. And these are concerns that weigh heavily on a man who”s been diagnosed with prostate cancer."

Misconceptions about the severity and longevity of those side effects, too, may prevent a man from proceeding with appropriate treatment, says Sanda. "In some cases, men may turn to new and untested prostate cancer treatments under the erroneous assumption that something new will be better than refined surgical or radiation techniques that have been improved through years of experience," he says.

For example, surgical side effects like urinary leakage or incontinence can be common initially following the procedure. However, those side-effects are usually only temporary, and how long they last Ð may vary from one individual to another. In fact, the majority of men do recover their urinary control several months after surgery.

In contrast, radiation side-effects on sexuality or bowel functioning can develop over several months or years. Seed implants, touted as symptom-free when they were first introduced, are now known to be associated with similar side effects as those seen after either external radiation or surgery, says Sanda. He hopes that by conducting a national study on quality of life after prostate cancer treatment with several leading medical centers, they will be able to correct some of the misinformation about refined existing treatments, and place the untested promises of newer treatments in the appropriate context.

The study will monitor the men and their partners' quality of life following treatment, and carefully measure how the patients are doing at the time they started their prostate cancer treatment, from the perspective of other health concerns. The information gathered from the study will help better inform patients who are facing prostate cancer treatment about what outcomes they can expect in terms of their sexuality and urinary, bowel and rectal functioning following treatment.

"After prostate cancer treatment, men and their partners can certainly look forward to resuming their sexuality, to having fulfillment and pleasure in their sex life, and having other aspects of their quality of life aside from sexuality returned to the same levels before their treatment," says Sanda. "In terms of their sexuality, men may need to make some adjustments or accommodations," he continues. "But the ability to get some pleasure out of sex and to enjoy each other certainly is something that most men can look forward to after their treatment."

To learn more about the Urologic Oncology Program at the U-M Comprehensive Cancer Center, visit them on the web.

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Drug Developed for Rare Disease May Help Millions More as Cancer Treatment

UMHS researchers leading dozens of studies on anti-angiogenesis drug

An anti-angiogenesis drug developed at the University of Michigan is showing promise in studies of three different disease families, including multiple forms of cancer. The drug, tetrathiomolybdate or TM, essentially wages war against copper, which serves to choke off tumor growth, fibrosis and inflammation.

U-M researcher George Brewer, M.D., who developed the drug, presented his ongoing basic and clinical TM research at the 226th American Chemical Society national meeting Sept. 10, 2003.

TM began as a treatment for Wilson's disease, a rare genetic disease that causes toxic build-ups of copper. Brewer and colleagues realized the key role of copper in angiogenesis the formation of new blood vessels. In cancerous cells, the angiogenesis process runs uncontrolled. This led them to begin exploring TM applications for cancer treatment.

"TM inhibits angiogenesis and growth factor by reducing the copper," says Brewer, the Morton S. and Henrietta K. Sellner Emeritus Professor of Human Genetics at the University of Michigan Medical School. "Essentially, the drug blocks the key signaling pathway, preventing tumor cells from sending signals to form new blood vessels, which thereby prevents or slows the cancer from growing or spreading."

Brewer began developing TM as an anti-angiogenesis drug. He first partnered with breast cancer researchers, particularly Sofia Merajver, M.D., Ph.D., at the U-M Comprehensive Cancer Center. In 2000, they published promising results of a pilot clinical trial. From there, additional trials have followed, some of which are now reporting positive early results. In addition to breast cancer, Brewer is exploring TM treatments for kidney, liver and esophageal cancer. Currently, TM is involved in nine phase II clinical studies related to cancer, several of which are still recruiting patients. And more trials are planned.

For more information on TM research at the University of Michigan Comprehensive Cancer Center, call the Cancer AnswerLine™ at 1-800-865-1125; or visit them on-line.


To read more about these or other current research findings at the U-M Comprehensive Cancer Center, visit the News Releases section.

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This article is part of the Cancer Center's News Archive, and is listed here for historical purposes.

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