Shortened HER2 Gene Responds to Lapatinib but not Trastuzumab
According to a study published in the Journal of the National Cancer Institute, breast cancer cells expressing a shortened form of the HER2 gene can be treated with lapatinib, but they are resistant to another drug known as trastuzumab.
HER2 is a gene in the epidermal growth factor receptor family that plays a role in regulating cell growth. In about 15 to 20 percent of breast cancers, HER2 is overexpressed, and women with these kinds of tumors have a worse than average prognosis. Many breast cancers that express HER2 are resistant to the HER2 antibody trastuzumab, a drug often used to treat HER2-positive breast cancer. Some are resistant because they express p95HER2, a shortened form of the receptor that cannot bind to trastuzumab.
Maurizio Scaltriti, of the Vall d'Hebron University Hospital and Research Institute in Barcelona, and colleagues compared how tumors expressing p95HER2 and those expressing HER2 responded to treatment with trastuzumab or lapatinib, another drug for treating HER2-positive breast cancer. The researchers measured the growth of breast cancer tumors in mice treated with each drug. They found that p95HER2-expressing tumors were resistant to trastuzumab but responded to treatment with lapatinib.
"Our findings support that further characterization of HER2 expressing breast tumors, based on the presence or absence of p95HER2, may assist in the selection of the appropriate anti-HER2 therapy," the authors write.
Journal of the National Cancer Institute, April 18, 2007