BRAF V600E mutations are associated with poor prognosis in colorectal cancer. A study by Coffee and colleagues examined PI3K/mTOR signaling in BRAF V600E colorectal cancer cell lines after BRAF inhibition as well as cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition.
Western blot analysis showed sustained PI3K/mTOR signaling after BRAF inhibition. In a novel genetically engineered mouse model for BRAF V600E colorectal cancer, mice developed sessile serrated adenomas/polyps similar to those in humans. Combination treatment with BRAF and PI3K/mTOR inhibitors resulted in induction of apoptosis and tumor regression.
The investigators stated, “We have established a novel [genetically engineered mouse model] to interrogate BRAFV600E [colorectal cancer] biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials.” ■
Coffee EM, et al: Clin Cancer Res 19:2688-2698, 2013.