Researchers find targeted therapy combination overcomes treatment resistance in liver cancer

Researchers at the University of Pennsylvania School of Medicine and Abramson Cancer Center reported today at the annual meeting of the American Association for Cancer Research that combining two targeted therapies overcomes treatment resistance in liver cancer cell lines. The team is currently designing a trial to test the combination in patients.

Liver cancer is resistant to many chemotherapies and to cell-death inducing agents. Last year, however, 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.

Unfortunately not all patients respond to sorafenib and the drug does not cure the disease.

Therefore, Wafik El-Deiry, MD, PhD, Professor of Medicine, Genetics, and Pharmacology, and co-Program Leader of Radiation Biology in the Abramson Cancer Center, and colleagues have tested other targeted agents in combination with sorafenib.

They found that treating liver cancer cells with sorafenib and 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,” Dr. El-Deiry said. “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.”

The combination works regardless of whether the researchers use a monoclonal antibody that stimulates the TRAIL receptor, which resides on the surface of the cancer cells, or the receptor’s natural ligand, a small protein called TRAIL. Both the antibody and the TRAIL ligand are currently being tested as single agents in patients.

Within the next several months, Dr. El-Deiry’s team expects to announce the details for a trial testing the combination in patients.

In a healthy individual, the immune system 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, according to Dr. El-Deiry. His team found that sorafenib reduces the amount of Mcl-1 in the cancer cells, restoring their sensitivity to TRAIL-induced cell death.

Although the Penn investigators focused their current report on liver cancer, they discovered that the sorafenib-TRAIL combination also kills colon cancer cell in vitro and in animal models.

Source: University of Pennsylvania

Related stories:

Novel strategy under study for aggressive leukemia
A novel strategy to hopefully beat into oblivion one of the most aggressive forms of acute myelogenous leukemia combines the strengths of some of the newest leukemia agents, researchers say.
Penn researchers identify new combination therapy that promotes cancer cell death
Philadelphia -- Researchers at the University of Pennsylvania School of Medicine identified a combination therapy as a way to sensitize resistant human cancer cells to a treatment currently being tested in clinical trials They propose that the therapy may help to selectively eliminate cancer cells while leaving healthy cells intact, providing a cancer treatment with fewer side effects. The Penn team reports their findings in the July issue of Cancer Cell.
Researchers hot on the trail of brain cell degeneration
A research team headed by Academy Research Fellow Michael Courtney has identified a new molecular pathway in neurons. The pathway is a factor in the degeneration of brain cells, which in turn plays an important role in neurological conditions and diseases, such as Alzheimer's disease, epilepsy and stroke.
Cancer-killing invention also harvests stem cells
Associate Professor Michael King of the University of Rochester Biomedical Engineering Department has invented a device that filters the blood for cancer and stem cells. When he captures cancer cells, he kills them. When he captures stem cells, he harvests them for later use in tissue engineering, bone marrow transplants, and other applications that treat human disease and improve health.
Scientists find cancer cell defense method
A Seoul, South Korea, research team says it's identified the defense mechanism used by cancer cells to fight therapeutic chemicals.
Purdue scientists treat cancer with RNA nanotechnology
Using strands of genetic material, Purdue University scientists have constructed tiny delivery vehicles that can carry anticancer therapeutic agents directly to infected cells, offering a potential wealth of new treatments for chronic diseases.
Older renal cancer patients appear to benefit from sorafenib treatment
Older and younger patients with renal cancer derive similar benefit from sorafenib therapy and tolerate the drug equally well, according to a study published online October 7 in the Journal of the National Cancer Institute.
Mayo Clinic estimates new, tiny, super-sensitive probe could cut colon polyp removal in half
Based on results of a landmark study, researchers at Mayo Clinic's Florida campus see a future in which virtual biopsies will eliminate the need to remove colon polyps that are not cancerous or will not morph into the disease.

News discussion:

Medicine & Health news