Study Finds Possible Reason for Liver Cancer Treatment Setbacks

Epidermal growth factor receptor (EGFR), the human protein which controls cell growth, is often mutated by cancer and found to exist in excessive numbers in cancerous cells. These attributes have made it the target of several liver cancer therapies recently in development. Research from the Medical University of Vienna (MUV) has found that a misunderstanding of EGFR and improper patient selection is causing disappointing results in early clinical research.

A few years ago, researchers discovered the existence of high levels of EGFR in liver malignancies and targeted its specific promotion of cancer growth. Their efforts, however, proved largely unsuccessful.

Scientists at MUV sought to study the exact mechanics of EGFR and isolated the problem with existing research and drug development. They used mouse models and suppressed EGFR in several different hepatic cell types.

Their research found that tumor growth was reduced when EGFR was suppressed in immune cells or microphages triggered by inflammations or infections.

In a report published in Science Daily, Maria Sibilia, coordinator of the project, explains, “In this study we were able to prove that the inhibition of EGFR has a tumor-inhibiting effect on the macrophages and not its inhibition on the tumor cell itself.”

Karin Komposch, another researcher on the project, adds, “We were able to show that injuries to hepatocytes trigger the release of the messenger substance, interleukin-1 beta. This, via diverse intermediate stages, causes EGFR in liver microphages to stimulate the production of interleukin-6, which causes liver cells to proliferate.” A process which should lead to the repair of damaged tissue can also promote tumor growth.

Therefore, the scientists concluded that EGFR targeting therapies would only be effective in patients who presented with an excess of EGFR in their immune cells. The research team hopes that this new information can redirect existing research and drug development by enhancing our understanding of complex cellular signaling pathways.

Their findings were the result of a project funded by the Austrian Science Fund FWF doctoral program and were recently published in NATURE Cell Biology.

The American Cancer Society reports that 700,000 people worldwide are diagnosed with liver cancer each year. Because current treatment options are so limited, prognosis for these patients is very poor. Liver cancer is the leading cause of cancer related death.