NEW YORK (Reuters Health) - A new monoclonal antibody against ErbB2, known as 2C4, inhibits the growth of breast tumors that express low and high levels of ErbB2 and the growth of prostate tumors that are resistant to hormone blocking drugs, animal study findings indicate.

Trastuzumab (Herceptin), an anti-ErbB2 antibody, has been shown to be an effective treatment for breast cancer. However, the drug only works against tumors that express high levels of ErbB2. Similarly, while trastuzumab has been shown to inhibit the growth of testosterone-dependent prostate tumors, it has little effect on testosterone-independent tumors.

In the current study, Dr. David B. Agus, from Cedars-Sinai Medical Center in Los Angeles, and colleagues tested the efficacy of 2C4 against cancer cell lines in culture and against breast and prostate human tumors grown in mice. The findings are published in the August issue of Cancer Cell.

Like trastuzumab, 2C4, which is produced by San Francisco-based biotechnology company Genentech, Inc., targets ErbB2. However, the current findings indicate that 2C4 disrupts ErbB2's association with the other ErbB receptors, while trastuzumab does not.

"This means that 2C4 has the potential to turn off the entire ErbB-kinase signaling axis in solid tumors, as most solid tumors have ErbB2 on their cell surface, which is integral in the cell's signaling apparatus," Dr. Agus said in a news release.

In a murine model of breast cancer, the researchers found that 2C4 dramatically inhibited the growth of tumors, regardless of how much ErbB2 was expressed by the cancer cells. In agreement with previous reports, trastuzumab was only effective against tumors that expressed high levels of ErbB2.

"These findings...may ultimately mean that we can treat more patients with breast cancer," Dr. Agus pointed out.

Furthermore, 2C4 was found to inhibit the growth of testosterone-dependent and testosterone-independent prostate tumors. In contrast, trastuzumab was only effective against testosterone-dependent tumors.

"The potential of a biologic agent, such as 2C4, to treat advanced prostate cancer is exciting, as there are presently few alternatives for treatment in these patients," Dr. Agus added.

A phase I clinical trial of the drug in patients with advanced cancers of the prostate, breast, ovary, lung, colon, and other solid tumors is currently underway.

Cancer Cell 2002;2:127-137.

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