Mesothelioma is a rare, incurable cancer of the lining of the lungs, heart and abdomen that is caused by past exposure to asbestos. The cancer is extremely aggressive making treatment challenging. However, researchers agree that understanding how to stop metastasis is critical for increasing survival in mesothelioma patients. The same is true of other cancers, but blocking the growth of tumors has been elusive and has remained a key focus of cancer research. Now, researchers at UT Southwestern Medical Center report they have successfully blocked tumor development of an incurable cancer, effectively demonstrating a cure.
The researchers developed a genetic mouse model of untreatable malignant peripheral nerve sheath tumors, a form of cancer of the connective tissue surrounding nerves, to conduct their study. They showed that by blocking the activity of a receptor molecule named CXCR4 they were able to inhibit tumor development.
“To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor,” said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study.
The National Institutes of Health reports that mouse models are critical in medical research. The models “that recapitulate many aspects of the genesis, progression, and clinical course of human cancers are valuable resources to cancer researchers engaged in a variety of basic, translational, clinical and epidemiological investigations.”
According to the study published in Cell, the researchers found that CXCR4, a protein essential for tumor growth, is more abundant in cancerous cells than in precursor cells. They also found that a molecule produced by the cancer cells themselves, CXCL12, works with CXCR4 to stimulate yet another protein that causes the cells to split and divide, thus stimulating more growth.
Through both genetic manipulation and injection of an FDA-approved antagonist drug for CXCR4 the researchers were able to inhibit the cancer growth. The approach was less effective in tumors without the increased expression of CXCR4.
“We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today,” said Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology.
Researchers from the University of California published a separate study reporting that CXCR4 and CXCL12 proteins “are highly expressed in most mesothelioma cell lines and tumor tissues, suggesting that CXCR4 and CXCL12 may be used as biomarkers for patients with mesothelioma. The CXCL12-CXCR4 interaction may be a potential therapeutic target for mesothelioma.”
Targeted, personalized therapy based on a patient’s unique mesothelioma characteristics, such as expression of certain biomarkers like CXCR4, optimizes the potential for success of the treatment and offers treatment options that may not otherwise have been considered.
Mesothelioma, caused by asbestos exposure, is diagnosed in close to 3,000 Americans each year. Currently there is no cure for the disease, but research into treatments of other cancers is followed closely by the mesothelioma community in hopes the results are transferrable to mesothelioma patients.
The UT Southwestern Medical Center researchers are currently planning human trials.