Chemotherapy for mesothelioma patients has been notoriously difficult and the cancer continues to be overwhelmingly unresponsive to such treatment in many cases. However, researchers and scientists have been continually investigating new techniques that involve adjusting how chemotherapy reacts on a cellular level. A study published in the Frontiers in Pharmacology examines a specific enzyme that is believed to cause increased cellular growth in mesothelioma patients and studies how its blockage can provide mesothelioma patients with chemotherapy that is actually effective.
AXL is a gene that encodes receptor tyrosine kinase to block the action of an enzyme. It can be found on the surface of cells and acts as a defense, protecting the cells from anything deemed abnormal, including chemotherapy treatments. In mesothelioma patients, AXL kinase expression is high, so chemotherapy treatments are not as effective in this already aggressive cancer. Additionally, asbestos and chemotherapy can produce increased reactive oxygen species molecules which can also result in high AXL expression. Scientists and researchers from the University of Kansas, New Mexico, and Hungry investigated AXL inhibitor BGB324 to determine if lowering AXL gene expression would allow the patient to be more responsive to first line chemotherapy treatments cisplatin and pemetrexed. Inhibitor BGB324 has been used in lung cancer and acute myeloid leukemia patients and has showed favorable results.
When introduced to mesothelioma cells, the cells became more responsive to the chemotherapy treatment, especially when the cells were introduced to BGB324 before chemotherapy was administered. This suggests that a chemotherapy regimen combined with AXL inhibition can increase effectiveness of cisplatin and pemetrexed in mesothelioma. Often times, chemotherapy is the first line of treatment to be applied to mesothelioma patients because of how advanced the disease typically is by the time it is diagnosed. Surgery is one of the more successful treatments, but unfortunately it can only be the most effective in the early stages of mesothelioma.
A mesothelioma diagnosis typically occurs decades after initial exposure, some upwards of 40 years. Those suffering are more often than not the elderly, and in a position where they are not able to fight cancer as well as they might have been able to be at a much younger age. Chemotherapy can be effective, but its overall toll on the body can leave the patient in a weakened state. Treatments that help boost the positive effects of chemotherapy are obviously favorable, and by inhibiting AXL, those beneficial effects are highlighted.
Oien, DB, et al, “Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy,” Frontiers in Pharmacology (January 11, 2018). [Link]