Biomarker Predicts Breast Cancer Resistance

Activation of signaling pathway predicts trastuzumab resistance

FRIDAY, Oct. 19 (HealthDay News) -- Activation of a cellular signaling pathway is an effective biomarker for trastuzumab resistance in breast cancer, according to a report published in the Oct. 16 issue of Cancer Cell.

Katrien Berns, Ph.D., from the Netherlands Cancer Institute in Amsterdam, and colleagues performed a large-scale RNA interference screen (targeting about 8,000 genes) to identify genes involved in trastuzumab resistance in breast cancer cells.

The researchers found that loss of expression of the PTEN gene led to trastuzumab resistance, even though this gene is lost in only a fraction of breast cancers. Further investigation showed that a mutant of the PIK3CA gene, which is frequently mutated in breast cancers and is part of the PI3K signaling pathway upstream of PTEN, also led to trastuzumab resistance. An analysis of 55 breast cancer patients showed that prognosis was poor after trastuzumab treatment in patients with activation of the PI3K pathway.

"Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy," Berns and colleagues conclude.

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