How HXR9 Could Lead to a Better Mesothelioma Treatment

Treatment // May 24, 2016

Cancer research is honing in on a new possible target for mesothelioma treatment. A new drug, aimed at cell receptors in the HOX family, has shown promise in both mouse xenograft models and in-vitro cell culture models. A recent study published in BMC Cancer shows that the novel drug, called HXR9, can selectively kill cancerous cells through a process called apoptosis.

All types of cancer, including mesothelioma, are triggered by a lack of balance in cells’ normal growth processes. Some genes control cell division and cell growth, and other genes control cell death via a “self-destruct” sequence, or apoptosis, when the cell is damaged or infected. Mutations in these “control genes” are often triggered by external factors such as exposure to chemicals, radiation, or in the case of mesothelioma, microscopic asbestos particles.

The researchers behind the BMC Cancer article focused on a family of genes known as homeobox, or “HOX” genes, which play a prominent role in embryonic development, where they regulate the organization of the organism’s body plan. HOX genes continue to function in the adult body. They regulate cell death by controlling apoptosis, and mutations in the HOX family are known to be involved in several different types of cancer.

The newly published research suggests that mesothelioma tumors in particular have a higher-than-normal expression of one specific HOX gene, called HOXB4. When the scientists measured HOX genes in mesothelioma cell culture lines and in tumor tissue samples from 16 mesothelioma patients, they found a significantly higher expression of HOXB4 than in normal, non-cancerous mesothelial cells.

Not only is HOXB4 associated with mesothelioma tumors, but the scientists discovered that the level of HOXB4 expression in the tumors they tested correlated with the median survival of the patients. Higher expression of the gene meant a more aggressive cancer and a poorer prognosis. The research suggests that future genetic testing of patients’ mesothelioma tumors can help to better predict the course of their disease.

A mesothelioma-specific marker also means the possibility of a mesothelioma-specific drug. The drug tested in this study, HXR9, is an excellent candidate as a new treatment for mesothelioma. HXR9 was specifically designed to block cellular HOX receptors, including HOXB4. When the researchers tested the drug on three different mesothelioma-derived cell cultures in-vitro, they saw an increase in apoptosis in all three of the cell lines. The cell lines with the highest expression of HOX genes were the most sensitive to the drug, and were more likely to be destroyed by exposure to HXR9.

Researchers then tested the HXR9 on a mouse in-vivo model. Mice were given a simulated version of mesothelioma by having human mesothelioma tumors grafted inside their bodies, and they were split into treatment and control groups. The mice who received injections of HXR9 saw their tumors grow much more slowly than the control group. The untreated mice, who were only given a saline solution, showed a “significant, linear relationship between the expression of HOXB4 and final tumor size,” supporting the findings reported in the human biopsy samples.

In the end, the researchers concluded that “targeting the interaction between HOX proteins and their PBX cofactor causes apoptosis in mesothelioma cells in vitro and retards tumor growth in vivo, indicating that HOX proteins are a potential therapeutic target in this malignancy.”

Those results are encouraging news, even though the study size was small. Targeted treatments aimed at specific gene mutations are the most promising future weapons in the fight against cancer. Finding a target specific to mesothelioma cells is a huge step towards perfecting a drug that can give patients a better chance.