Researchers confirmed in a new study that HOX genes are potential therapeutic targets for the treatment of mesothelioma, and demonstrated that a new drug, HXR9, successfully halted tumor growth and induced apoptosis in human mesothelioma tumors in a mouse model — the first time a drug has been found to induce programmed cell death in mesothelioma.
The paper, by scientists at the universities of Bradford and Surrey in the U.K., is titled “HOX transcription factors are potential targets and markers in malignant mesothelioma,” and was published in the journal BMC Cancer.
Mesothelioma is a rare but aggressive cancer, and malignant mesothelioma, despite efforts at effective therapeutic strategies, remains stubbornly resistant to existing treatments — namely, radiation and chemotherapy. According to the Mesothelioma Cancer Alliance, only 5 percent to 10 percent of mesothelioma patients live five years after diagnosis, and about 43,000 people worldwide die from the disease each year.
Researchers assessed the role of the HOX gene family in mesothelioma and the effectiveness of a drug they developed, HXR9, that targets these genes. HOX genes are involved in the rapid cell division observed in embryos, and are usually switched off in adults. However, previous research has shown that many cancers have active HOX genes, which help these cells survive and proliferate. Analysis of mesothelioma-derived cell lines and patient tumors showed that HOX genes are significantly dysregulated in malignant mesothelioma, and that one gene in particular, HOXB4, is strongly associated with overall survival. Specifically, the more HOXB4 protein found in a patient’s tumors, the less time that person survived. Such findings constitute a new possible method for determining the cancer’s aggressiveness.
In mice models with human mesothelioma tumors, researchers observed that three-week treatment with the drug HXR9 was successful in preventing the growth of mesothelioma, and caused apoptotic cell death in all mesothelioma-derived cell lines. Apoptosis is a natural sequence instructing damaged or harmful cells to die, and to which cancers have developed evasion mechanisms.
“There’s a range of drugs which try to force apoptosis in different cancers, but this is the first one to work in mesothelioma,” Professor Richard Morgan, director of the University of Bradford’s Institute of Cancer Therapeutics, who also developed the drug and led the study, said in a press release. “We’ve effectively knocked out a key defence mechanism in this cancer through targeting the HOX genes.”
Mesothelioma affects the mesothelial cells, which form a thin layer that covers, protects, and lubricates serous cavities, consisting of the membranes pleura (lungs), pericardium (heart), and peritoneum (abdomen), as well as the surfaces of internal organs. The incidence of this cancer has grown in the last decades, mainly due to past exposure to asbestos, one of its main risk factors.