The researchers found that targeting HOX genes with the drug HXR9 triggered the death of cancer cells in mesothelioma.
Researchers from the Universities of Bradford and Surrey in the UK report their findings in the journal BMC Cancer.
The body has a natural process for shutting down damaged cells. HRX9 works by ensuring cancer cells cannot get around this, as lead researcher Richard Morgan, a professor in Bradford’s Institute of Cancer Therapeutics, explains:
“Both the immune system and nearby healthy cells send signals instructing damaged and unhealthy cells to undergo apoptosis, which is like programmed ‘cell suicide.’ But cancer cells have developed a wide range of strategies to ignore these instructions.”
Prof. Morgan, who developed the drug, says there is a range of drugs that can trigger apoptosis, but HRX9 is the first one that works with mesothelioma.
Mesothelioma is a cancer that develops in the tissue that covers the surface of some organs in the body. It mainly arises in the lining of the lungs, usually as a result of exposure to asbestos.
The cancer is resistant to all current chemotherapies, and the prospects for patients diagnosed with it are very poor; few survive more than a year after diagnosis.
‘Knocks out key defense mechanism in mesothelioma’
In their study, Prof. Morgan and colleagues show that the HOX family of 39 genes is significantly dysregulated in malignant mesothelioma. HOX genes enable the really fast cell division that occurs in growing embryos.
The genes are normally switched off after embryo development, but previous studies have shown that in certain cancers – such as brain, prostate and ovarian cancers, plus melanoma and leukemia – the genes are switched back on again.
When they targeted HOX genes with HXR9, the team found it triggered apoptotic cell death in all the mesothelioma cell lines they tested, and it also prevented the growth of human mesothelioma tumors in mice.
The researchers found that after 3 weeks of treatment with HXR9, the human mesothelioma tumors in the mice stopped growing; there was a complete loss of tumor blood vessels and widespread death of cancer cells.
Prof. Morgan says targeting the HOX genes appears to knock out a key defense mechanism in the mesothelioma cells.
Predicting most aggressive form of mesothelioma
The study also reveals another important finding regarding a particular HOX gene called HOXB4. Prof. Morgan says HOXB4 appears to predict which patients have the most aggressive form of mesothelioma.
He and his colleagues measured levels of HOXB4 protein in mesothelioma tumors from 21 patients, and they found the more HOXB4 protein that was present, the shorter the survival time of the patient.
Even though it has been 30 years since asbestos use peaked in the US, over 3,000 Americans are diagnosed with mesothelioma every year, showing the population is still at risk.
Also, in Africa and some parts of Asia, where there is less awareness of its dangers than in the West, there is widespread industrial use of asbestos and workers who demolish buildings containing the natural fibrous rock are poorly protected.
Prof. Morgan says mesothelioma is still going to be a significant public health problem and, as it is resistant to available drugs, we need entirely new treatments.
Ian Jarrold, head of research at the British Lung Foundation, the charity that funded the research, says while it is still early days, the study is a significant step forward because it is the first time we have seen a drug triggering cell suicide in mesothelioma. He sums up the desperate need for effective treatments against this awful disease:
“People living with mesothelioma often tell us that among their first reactions to diagnosis is despair at the lack of treatment available. We hope that the progress being made in research we fund will soon provide new treatments and new hope for patients.”
Meanwhile, from another recently published study, Medical News Today learned that researchers have uncovered a spectrum of mutations in mesothelioma.
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