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Treatment delivers miRNA to late-stage liver cancer tumors with low toxicity.
Researchers were been able to deliver tumor suppressing therapies to patients with liver cancer using nanoparticles in a recent study.
Liver cancer develops from chronic liver disease and is the leading cause of cancer-related deaths. Approximately 20,000 men and 8000 women get liver cancer in the United States each year. According to the US Centers for Disease Control and Prevention, the 5-year survival rate is 17%.
Unfortunately, treating liver cancer can prove to be difficult because certain drugs that could help with treatment can cause devastating toxicity in cirrhotic livers with late-stage cancer. Liver cancer rates in the United States has been slowly on the rise for decades, with a higher percentage of diagnoses in Asian, Hispanic, and African American men.
In a study conducted by the UT Southwestern Medical Center published in the Proceedings of the National Academy of Sciences, researchers were able to create a synthetic “dendrimer” nanoparticle, which produced a tumor-suppressing effect without damaging the liver or surrounding tissue.
"We have synthesized highly effective dendrimer carriers that can deliver drugs to tumor cells without adverse side effects, even when the cancerous liver is consumed by the disease," said researcher Daniel Siegwart, PhD. "We found that efficacy required a combination of a small RNA drug that can suppress cancer growth and the carrier, thereby solving a critical issue in treating aggressive liver cancer and providing a guide for future drug development."
Investigators looked to develop non-toxic carriers as well as exploring “miRNA” alternative therapies. MicroRNAs are short nucleic acids that function as natural tumor suppressor, but require delivery strategies to transport these drugs into cells.
No existing carrier has been able to deliver medication to cancer cells without adding toxicity to the liver. The failure of five phase 3 trials that used small molecule drugs in order to treat hepatocellular carcinoma fueled the current study.
Scientists used genetic mouse models that had an aggressive form of liver cancer. By synthesizing more than 1500 different types of nanoparticles, they were able to discover lead compounds that functioned in the compromised cancerous liver.
With the dendrimers --- the synthetic nanoscale compounds --- they were able to screen different combinations of chemical groups, physical properties, and molecular size. This allowed them to identify dendrimers that could deliver miRNA to late-stage liver cancer tumors with low toxicity.
The researchers concluded that miRNA nanoparticles are able to stop tumor growth while extending survival rates.