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Monoclonal Antibody Induces Death in Liver Cancer Cells

Researchers at the University of Pittsburgh School of Medicine have found that a newly available monoclonal antibody has the potential to induce death in liver cancer cells.

In a study, the monoclonal antibodies' use demonstrated significantly reduces tumour cell proliferation and survival in human and mouse hepotocellular cancer (HCC) cell lines.

The researchers say that the new findings have significant implications not only for the treatment of live cancer, but also for various other types of cancer-skin cancer, brain tumours, gastrointestinal tumours, prostate tumours, ovarian cancer and leukaemia.

According to the background information in an article published in the journal published in Molecular Cancer Therapeutics, most cases of HCC are secondary to either a viral hepatitis infection or cirrhosis of the liver.

Despite recent advances, it remains a disease of grim prognosis due to the poorly understood mechanism of how the disease originates and spreads. Most patients live only a short time after diagnosis.

Dr. Satdarshan P. Singh Monga, Associate Professor in the division of cellular and molecular pathology at the university, directed his colleagues to obtain rat and human liver cancer cell lines so as to analysed the cell lines for the levels of expression of an receptor tyrosine kinase (RTK) protein, shown to be highly active in the liver of HCC patients in some previous studies, known as platelet-derived growth factor receptor-alpha (PDGFRa).

The researchers also analysed the cells for their level of activation of the PDGFRa gene.

It was found that at an early foetal stage of liver development in the mouse, the level of expression of PDGFRa was 37 times higher compared to later stages of development in the adult mouse liver. The researchers also found significantly higher levels of PDGFRa in rat and human liver cancer cell lines as compared to normal ce lls in culture.

When both human and mouse live cancer cell lines were treated with a monoclonal antibody, tumour cell proliferation significantly decreased and programmed cell death (apoptosis) increased four to 18 fold, as compared to normal control cells.

The researchers say that the results depict PDGFRa as a possible new therapeutic target for the treatment of HCC.

"We are very excited because this is the first targeted therapy for liver cancer. Other therapies have some modest benefits, but no one knows exactly how they work. We now have identified a pathway that appears to be overly active in more than 70 per cent of the cancers we examined and, when targeted, leads to significant reduction in tumour cell proliferation and survival," said Dr. Monga.

He also says that targeting the PDGFRa pathway in liver cancer cells does not affect normal liver cells, making the treatment relatively non-toxic.

"Normally, regenerating liver cells are not exclusively dependent on this pathway, and it is not overly active in other types of cells. So this monoclonal antibody is a highly targeted treatment for this disease," he added.


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