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Asking Why Breast Cancer Drug Herceptin Works

By Kate Ruder

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Breast Cancer

Some breast cancer patients respond remarkably well to the drug Herceptin, but the drug doesn’t seem to work at all for others. Now, scientists have discovered that a specific protein in tumors may be a good predictor of whether Herceptin will be effective against the cancer.

Patients in the study who responded to the drug had normal amounts of the protein, while those who did not had low levels of the protein. The researchers concluded that the protein, called PTEN, helps Herceptin fight tumors, and that the loss of PTEN makes tumors resistant to the drug.

Herceptin is part of a relatively new class of drugs that target specific genes in cancer cells. The drug is usually given to women who have accumulated extra copies of a gene called HER-2 in their tumor cells. Yet only 35 percent of these women respond to the drug, and some have severe side effects.

In an effort to understand resistance to the drug, scientists at M.D. Anderson Cancer Center in Houston, Texas, analyzed the tumors of 47 patients who had received Herceptin plus chemotherapy. They found that tumors that lacked PTEN did not respond as well to the drugs as tumors with PTEN.

Then, in breast cancer cells in the laboratory, they found that reducing the amount of PTEN made cells resistant to Herceptin (also known as trastuzumab).

“In general, what we need to do in the context of Herceptin treatment is take a closer look at all the players that may lead to resistance,” says Matthew Ellis of Washington University School of Medicine and Siteman Cancer Center in St. Louis Missouri. Ellis was not involved with the study and co-authored a commentary that accompanies the paper in Cancer Cell.

At the moment there is no commercially available test to detect the level of PTEN in tumors, and it could be years before such a test is developed, if one ever is. Still, the hope among many researchers is that studies such as this one will lead to the day when a person’s tumor is analyzed genetically as part of the treatment process.

“We want to understand aberrations in the genomes of cancer cells in order to customize the treatment decisions,” says Ellis.

Nagata, Y. et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6, 117-127 (August 2004).
Crowder, R. J. et al. Successful targeting of ErbB2 receptors—is PTEN the key? Cancer Cell 6, 103-104 (August 4, 2004).

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