Overexpression of p27 Inhibits HER-2 in Preclinical Tests

WASHINGTON—About 30% of breast cancer patients show overexpression of the HER-2/neu oncogene, and trastuzumab (Herceptin), a monoclonal antibody targeting HER-2, has been shown to block the gene’s receptor activity. But because the response rate to trastuzumab "is not ideal," there is "still a need for a better therapeutic agent" aimed at HER-2, said Mong-Hong Lee, PhD, assistant professor of molecular and cellular oncology, M.D. Anderson Cancer Center.

Speaking at the Susan G. Komen Breast Cancer Foundation’s 5th Annual Conference on Innovations in Quality Care, he described progress on another approach: exploiting the ability of the p27 gene, a "negative regulator of the cell cycle," as a brake on cells that overexpress HER-2. Just as overexpression of HER-2 correlates with poor prognostic outcomes, so does reduced expression of p27, especially in young women, Dr. Lee said. The inverse relationship between these two markers suggests a possible therapeutic approach, he said. He noted that this relationship was earlier established by his former lab members Hong-Yin Yang, PhD, and Lisa Newman, MD.

Preclinical testing has shown that p27 can reverse the transformation phenotypes of cancer cells overexpressing HER-2 and that p27 has potential as a novel tumor suppressor. To maintain suppression, p27 would have to be "continually supplied," Dr. Lee said. Various methods of delivering the gene, including adenovirus and liposomes, are currently being investigated.