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Old 08-24-2004, 08:44 AM   #1
Merridith
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Aug 23/04

Researchers discover new tumor-fighting ability in popular breast cancer drug

Results may help further target drug to patients most likely to benefit

For many patients with advanced breast cancer the cancer drug Herceptin (trastuzumab) has offered new hope when traditional cancer drugs failed to work shrinking tumors and sending some patients into remission.

Now Dihua Yu M.D. Ph.D. and her colleagues at The University of Texas M. D. Anderson Cancer Center have uncovered a powerful new cancer-fighting property of Herceptin an antibody-based drug that targets a protein on breast cancer cells called HER-2 (also called ErbB2). The discovery explains why some HER-2 positive patients don't respond as well to the drug and also offers a potential solution that could allow more HER-2 positive patients to benefit from the treatment.

The study which appears in the August 2004 issue of the journal Cancer Cell demonstrates that the presence of a protein called PTEN in HER-2 positive patients' tumor cells is a powerful predictor of who will respond to Herceptin. In normal cells the PTEN protein helps control cell division but in about half of breast tumors PTEN levels are very low or the protein is completely missing. Those PTEN-missing tumors did not respond to Herceptin treatment.

"Our goal is to allow doctors to quickly and accurately tailor cancer treatment to each individual patient " says Yu professor of surgical oncology and the study's principal investigator. "Tailored treatment means giving each patient the medication most likely to benefit her while simultaneously minimizing side effects."

In a recent clinical trial at M. D. Anderson 65 percent of HER-2 positive patients taking Herceptin in addition to chemotherapy had a complete response rate compared to 26 percent taking chemotherapy alone. But doctors have had no way to predict who among HER-2-positive patients which account for about one-third of all breast cancer patients is most likely to benefit.

"Previously it was known that Herceptin binds to the HER-2 protein and causes it to degrade " says Yu. "But this process takes days. What we found is that very quickly within ten minutes of administration Herceptin activates PTEN a powerful tumor suppressor gene. We are adding a very new understanding of how Herceptin works."

The scientists studied the tumors of 47 metastatic HER-2 positive breast cancer patients who had received Herceptin and chemotherapy as well as 37 patients who received chemotherapy alone. PTEN levels varied widely among both groups but only 11 percent of patients who had a very low level of PTEN responded to Herceptin versus 66 percent of those with high levels of PTEN. There was no correlation between PTEN level and response to traditional chemotherapy agents called taxanes.

"Our results show PTEN is a very powerful predictor of who will respond to Herceptin " says Yu.

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