Penn researchers find targeted therapy combination overcomes treatment resistance in liver cancerApril 14, 2008SAN DIEGO -- 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. University of Pennsylvania School of Medicine | |||||||||||||||||||||
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Related Liver Cancer Current Events and Liver Cancer News Articles Hepatitis B exposure may increase risk for pancreatic cancer In a first-of-its-kind finding, researchers at The University of Texas M. D. Anderson Cancer Center have discovered that exposure to the hepatitis B virus (HBV) may increase the risk of pancreatic cancer. Gene variant boosts risk of fatty liver disease, scientists discover Researchers at UT Southwestern Medical Center have found that individuals who carry a specific form of the gene PNPLA3 have more fat in their livers and a greater risk of developing liver inflammation. To protect against liver disease, body puts cells 'under arrest' A stable form of cell-cycle arrest known to offer potent protection against cancer also limits liver fibrosis, a condition characterized by an excess of fibrous tissue, according to a new report in the August 22nd Cell, a Cell Press publication. Senescence in liver cells is found by CSHL scientists to help limit acute tissue damage Although post-reproductive life in humans is often associated with decline and a loss of powers, an analogous state in certain cells -- called senescence -- is proving to be one of ironic potency. Scientists at Cold Spring Harbor Laboratory (CSHL) today reported that a particular class of senescent liver cells orchestrates a sequence of events in living mice that can limit fibrosis, a natural response of the liver to acute damage. New study finds advanced liver cancer patients live longer by taking anti-cancer drug sorafenib Researchers at Mount Sinai School of Medicine in New York have found that sorafenib (Nexavar) helps patients with advanced liver cancer live about 44 percent longer compared with patients who did not receive the anti-cancer drug. Predicting acute GVHD by gene expression could improve liver stem cell transplant outcomes Many cell transplants involve the use of stem cells from another human being (known as an allograft), which raises the major concern of the potential for acute graft-versus-host disease (GVHD). Hepatitis C virus may need enzyme's help to cause liver disease A key enzyme may explain how hepatitis C infection causes fatty liver - a buildup of excess fat in the liver, which can lead to life-threatening diseases such as cirrhosis and liver cancer, report University of Pittsburgh Graduate School of Public Health and School of Medicine researchers. New therapy shows promise for fighting treatment-resistant cancer cells A gene radiotherapy system that detects and treats cancer cells that are resistant to traditional forms of chemotherapy and radiation showed success in the laboratory and could eventually prove beneficial for cancer patients, according to researchers at SNM's 55th Annual Meeting. CSHL scientists trace causal link between a tumor suppressor gene and liver cancer Scientists at Cold Spring Harbor Laboratory (CSHL) have taken the search for cancer-causing genes an important step forward. In a newly published paper, they confirm that a gene called DLC1 is a tumor suppressor. They have demonstrated in living mice that its deletion, inactivation or loss precipitates events culminating in an aggressive type of liver cancer closely related to common human epithelial cancers of the liver (also known as hepatocellular carcinoma, or HCC). Study concludes no racial disparities in long-term outcomes in recipients of liver transplants New research published in the Journal of the American College of Surgeons shows long-term survival and liver rejection rates are equivalent for African-American liver transplant patients as compared with patients of other races. More Liver Cancer Current Events and Liver Cancer News Articles |
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