Lung Cancer has the highest mortality rate of all cancer and smoking remains the main cause behind this deadly disease. As far as the treatment options for lung cancer are considered, there are extremely limited and especially for patients with oncogenic mutations in KRAS gene. In a paper published in Science Translational Medicine, a MedUni Vienna research group led by Herwig Moll has identified a potential marker for success of immunotherapy in lung cancer patients. During the course of the study, they have discovered that enhanced sensitivity of cancer cells to immunomodulatory cytokine interferon gamma is primarily responsible for this.
K-RAS is a monomeric G protein that plays a pivotal role in growth of malignant tumors. KRAS-mutated lung carcinomas occur mostly in chronically inflamed lungs and this process promotes growth of cancer cells. The team has now shown the expression of highly anti-inflammatory protein A20 which is often very low in malignant cells. They have found that there is a direct correlation between a patient’s life expectancy and expression of A20 protein. The tumor cells with down regulated A20 responded well to immune checkpoint inhibitors in the same manner as patients suffering from skin cancer with a similar gene expression structure.
Herwig Moll said, “Both in humans and in the animal model, the loss of A20 leads to downgraded immune surveillance of cancer cells. Cancer cells with low levels of A20 are able to escape detection by the immune system.” The researchers would also like to find out whether it is possible to manipulate expression of A20 in cancer cells or not. This would help to intensify the effect of immunotherapy. According to the experts, it is important to continue to investigate new therapeutic approaches to improve the quality of life.
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