Agendia to develop microarray test for Herceptin resistance
Amsterdam – Researchers from Dutch Agendia BV have identified the tumor supressor PTEN (Phosphatase and Tensin homolog deleted on chromosome TEN) as a modulator of trastuzumab (Herceptin) resistance in breast cancer in a large-scale RNA interference screen. According to the researchers under Agendia’s CSO René Bernards, oncogenic mutants of PIK3CA, the activator of the phosphatidylinositol 3-kinase pathway, also conferred resistance to trastuzumab in cell culture (Cancer Cell. 2007 Oct;12(4):395-402). Agendia says the PI3K pathway is mutated in up to half of all breast cancer tumours.
Out of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy. The combined analysis of PTEN and PIK3CA also identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker signature to help identify patients unlikely to respond to trastuzumab-based therapy.
Agendia had acquired the rights to the discovery of the mechanism of Herceptin resistance. The company has announced it will develop a microarray-based diagnostic for identification of resistance-associated biomarkers. In another study (Proc Natl Acad Sci USA., Oct 29) the researchers identified retinoic acid signaling as a target of histone deacetylase inhibitors.