Combining two kinds of targeted agents—a PI3K/AKT inhibitor and agents that target epigenetic changes—may improve therapy for breast cancer in the future, according to researchers at Ohio State University.
They found that abnormal activation of the PI3K/AKT signaling pathway leads to the silencing of a number of tumor-suppressor genes that regulate cell proliferation, survival and motility, and angiogenesis (Cancer Res. Epub January 7, 2011).
Using the knowledge that activation of PI3K/AKT signaling can trigger epigenetic silencing at many downstream target genes and that DNA methylation can be acquired at the same loci in cancer cells, which reinforces permanent repression in those losing the H3K27me3 mark, Huang and colleagues combined these treatments. Their in vitro and xenographic models demonstrated that this combination synergistically relieved gene silencing and suppressed cancer cell growth.
The researchers suggest that the combination may offer a new therapeutic strategy for breast cancer. Huang and his colleagues are now planning a clinical trial for patients with metastatic breast cancer that will investigate the use of combined targeted drugs.