Therapy combo may overcome treatment resistance in liver cancer

Washington, Apr 14: Liver CancerPenn researchers have revealed that a combination of two targeted therapies can overcome treatment resistance in liver cancer cell lines.

Liver cancer is resistant to many chemotherapies and to cell-death inducing agents. The U. S. Food and Drug Administration approved sorafenib (Nexavar®) as a treatment for liver cancer after a clinical trial showed that the targeted agent prolonged survival in some patients, however not all patients could respond to the treatment.

In order to develop therapies to curtail resistance, team led by Dr Wafik El-Deiry, Professor of Medicine, Genetics, and Pharmacology, and co-Program Leader of Radiation Biology in the Abramson Cancer Centre tested other targeted agents in combination with sorafenib.

The findings revealed that by treating liver cancer cells with sorafenib along with an antibody or the natural ligand that stimulates programmed cell death via the TRAIL pathway, dramatically increases the rate of cell death.

“Sorafenib by itself causes a little cell death, but not that much,” said Dr. El-Deiry.

“Now you combine sorafenib and TRAIL, and all of the sudden you get massive cell death. It is a real synergistic interaction. It is very profound killing,” El-Deiry added.

According to him the immune system of a healthy individual uses the TRAIL pathway to rid the body of unwanted cells, including precancerous ones

Once cancer develops, however, the cells often become less responsive to TRAIL activation, in part because of an overabundance of a protein called Mcl-1.

The study found that sorafenib reduces the amount of Mcl-1 in the cancer cells, restoring their sensitivity to TRAIL-induced cell death.

The team is currently designing a trial to test the combination in patients.

The study was presented at an annual meeting of the American Association for Cancer Research. (ANI)