While the introduction of the drug Researchers Investigate Strategy to Prevent Resistance to Herceptin in Breast Cancer Patients (dateline January 16, 2002) | Breast Health News | Imaginis - The Women's Health & Wellness Resource Network

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Researchers Investigate Strategy to Prevent Resistance to Herceptin in Breast Cancer Patients (dateline January 16, 2002)

While the introduction of the drug Herceptin (generic name, trastuzumab) has been seen as a major advance in the treatment of advanced breast cancer, many breast cancer patients become resistant to the drug in approximately one year. In attempting to reduce patient resistance to Herceptin, researchers have recently found that decreasing the amount of a protein on many breast cancer cells called insulin-like growth factor 1 (IGF-1) enables Herceptin to destroy breast cancer cells for longer periods of time before the cells become resistant to the drug. The researchers believe their study opens doors for research into new drugs that work by blocking IGF-1. According to the researchers, these drugs could be used in combination with Herceptin to more effectively treat breast cancer.

Herceptin is approved by the U.S. Food and Drug Administration (FDA) for advanced (metastatic) breast cancer patients whose cancers have produced extra copies of the HER2 gene. HER2 (human epidermal growth factor receptor 2) is a gene found on the surface of cells that, when functioning normally, has been found to be a key component in regulating cell growth. However, when HER2 is altered, extra HER2 protein receptors may be produced. This over-expression of HER2 causes increased cell growth and reproduction, often resulting in more aggressive breast cancer cells.

Approximately 25% to 30% of breast cancer patients over-express the HER2 gene. Herceptin works by attaching itself to the HER2 protein receptors on the surface of breast cancer cells that over-express HER2. This process of binding to HER2 receptors slows the growth and spread of cancer tumors.

Using the concept of how Herceptin works, lead researcher Michael Pollack of the Jewish General Hospital in Montreal, Canada and his colleagues studied another growth factor found on many breast cancer cells called insulin-like growth factor 1 (IGF-1). IGF-1 is known to activate the survival signals of cancer cells and is thought to interfere with the effects of Herceptin on these cancer cells. Therefore, Pollack and his colleagues decided to reduce the amount of IGF-1 on breast cancer cells to determine whether they could boost the effectiveness of Herceptin. The result: reducing IGF-1 in breast cancer cells enabled Herceptin to decrease cell proliferation (the reproduction of breast cancer cells) by 42%.

To further investigate IGF-1 and Herceptin, the researchers gathered a different type of breast cancer cell that did not contain many IGF-1 receptors. When the researchers allowed Herceptin to reach these cancer cells, they found that the drug again decreased the proliferation of cancer cells by 42%. However, when Pollack and his team genetically altered these cancer cells to produce more IGF-1 receptors, they discovered that Herceptin did not have an effect on reducing cancer cell growth.

Thus, the researchers conclude that the development of new drugs to block IGF-1 receptors (and other similar receptors) on breast cancer cells could be effective in the fight against breast cancer. Specifically, these drugs could be used in conjunction with Herceptin to increase the overall effectiveness of Herceptin and reduce the chances that breast cancer patients will become resistant to Herceptin.

Currently, Herceptin is often used in addition to chemotherapy to improve its effectiveness. Though the drug is FDA-approved for advanced breast cancer patients, several clinical trials are currently investigating whether Herceptin is helpful in patients with early-stage breast cancer whose cancers over-express the HER2 gene. In fact, many experts believe that the future of cancer treatment lies in the development of more "target drugs" such as Herceptin that seek out and destroy certain parts of cancer cells, thereby preventing the cells from reproducing and surviving.

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