The investigational drug, called HXR9, targets the natural cell process called apoptosis, or programmed cell death.
According to researchers at the University of Bradford and University of Surrey who developed it, mesothelioma cells treated with HXR9 lose their ability to defy a natural death.
The Danger of Immortality
All healthy cells, including those of the pleural mesothelium (the lining around the lungs), eventually undergo apoptosis and are replaced by fresh cells.
But the same process that helps turn certain mesothelial cells into mesothelioma cells, also confers a sort of immortality, allowing these cells to grow out of control and form deadly mesothelioma tumors.
The process is controlled in part by a family of proteins known as HOX genes. Since HOX genes enable rapid cell growth in embryos, the research team reasoned, targeting them might help slow that growth in mesothelioma.
Targeting Genes to Slow Mesothelioma
To test the value of HOX genes as a target for mesothelioma treatment, Dr. Richard Morgan of the University of Bradford’s Institute of Cancer Therapeutics and his team first tested HXR9 on four different types human mesothelioma cells in the lab.
Next, they tested it in a mouse that had been infected with mesothelioma. After three weeks, the team evaluated the results.
“Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model,” writes Dr. Morgan in the British medical journal BMC Cancer.
Not only did HXR9 halt tumor growth, but it also wiped out the network of blood vessels supporting the mesothelioma tumor.
A Mesothelioma Prognostic Tool?
Another finding to come out of the HXR9 study was the fact that a particular HOX gene called HOXB4 was “strongly associated” with overall mesothelioma survival.
When Dr. Morgan and his colleagues measured levels of the HOXB4 protein in 21 different mesothelioma tumors, they found that mesothelioma patients with the highest levels had the shortest survival times.
The finding means that HOXB4 could be valuable as a way to help determine mesothelioma prognosis, which can be invaluable for treatment planning.
Mesothelioma, a fast-growing malignancy linked to asbestos exposure, claims the lives of approximately 2,500 people in the US each year and there is no cure.
Morgan, R, “HOX transcription factors are potential targets and markers in malignant mesothelioma”, February 11, 2016, BMC Cancer, p. 85