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Biomarkers with lapatinib could predict breast cancer response to treatment
Many patients do not respond to treatment, and biomarkers could spare them from the adverse effects related to chemotherapy.
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LOS ANGELES - New biomarkers associated with response to treatment with lapatinib and CI-1040 could help predict drug response in patients with breast cancer, according to research from the Lawrence Berkeley National Laboratory at the University of California-San Francisco.
Joe W. Gray, PhD, director of the life sciences division at the laboratory, and colleagues, evaluated drug response using a system of 50 breast cancer cell lines. They presented their data at the 2007 Annual Meeting of the American Association for Cancer Research.
"Individuals respond differently to different therapeutics because there are substantial differences in the spectrum of genetic, biological and epigenetic characteristics among breast cancers, although some recurrent abnormality patterns are emerging that define breast cancer subtypes," Gray said.
"We need better ways to identify how we can best tailor existing therapies to individuals and how to target experimental agents."
The researchers evaluated drug response using breast cancer cell lines that mirror the abnormalities and biological variability in primary tumors. The cell lines were analyzed for gene expression patterns, genome copy number abnormalities and protein abundances. Each cell line represented a variant in the genomic abnormalities in breast cancer.
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The researchers sought to correlate cell response to targeted therapies using the genomic signatures to identify response predictors. They assessed cell responses to lapatinib (Tykerb, GlaxoSmithKline) and CI-1040, an investigational MEK inhibitor. The researchers used a cell growth assay in microtiter format.
Mathematical analyses established associations between the molecular characteristics of the cell lines and their responses. According to these analyses, overexpression or amplification of ErbB2 correlated with sensitivity to lapatinib treatment. Similarly, phosphorylation of MEK enzyme and the levels of MAPK3 and AKT predicted response to CI-1040.
Although more validation is needed, these biomarkers could be used to prescreen patients before they receive therapy and define tailored treatments for patients. – by Emily Shafer
Dr. Gray received funding from GlaxoSmithKline.
For more information:
- Kuo WL, Guan Y, Hu Z, et al. Molecular predictors of drug response in breast cancer. # 4963. Presented at: 2007 Annual Meeting of the American Association for Cancer Research; April 14-18, 2007; Los Angeles.