Drug Targeting KRAS Mutation can Acts Against Lung Cancer Treatment

Release Date: 26-Sep-2019

The cases of lung cancer are increasing day by day. Lung cancer is the second most common cancer found in both men and women. It is estimated there will be roughly 228,000 new lung cancer cases this year. It is observed that nearly 30% of the patients with lung cancer will have mutations in the KRAS pathway. This type of mutation makes the cancer more aggressive and difficult to treat.

Researchers at Moffitt Cancer Center are working to target the KRAS pathway to prevent the mutation in lung cancer. In a new study published in Cancer Research, the team discovered a new treatment approach that may help this group of patients.

The KRAS is a gene is responsible for the regulation of the cell signaling, and results in the normal cell growth and division. The mutation in the KRAS gene results in the uncontrolled growth of the cells, as they starts ignoring the off signal. This is the main reason for the recent development in the field of KRAS inhibitors as possible therapeutic target.   

The researchers of Moffitt observed that the MEK kinase is also a possible target for the treatment of lung cancer. They found that the lung cancer cells treated with the MEK inhibitior trametinib in combination with cytokine TNF-alpha and IFNandgamma; results in the more cell death, as compared to the Mek inhibitor alone.

This study confirm that the MEK inhibitors increase the number of receptors on the cell surface for TNFandalpha; to bind, which leads to the delivery of a more potent and sustained cell death signal. IFNandgamma;, a cytokine known to be crucial for anti-tumor immunity, further enhances the anti-tumor activity of MEK inhibitors and TNFandalpha;. The MEK inhibitor also increases the expression of the target genes of TNF-alpha and IFNandgamma;, which results in the high anti-cancer immunity.

According to Amer A. Beg, Ph.D., senior member of the Immunology Department and Lung Cancer Center of Excellence at Moffitt and lead author of this study, MEK inhibitors alone do not provide strong overall response for this group of patients. He also added that Demonstrating an anti-cancer agent can so effectively modulate the activity of a cytokine signaling pathway crucial for so many biological processes is conceptually novel and can lead to new understanding of oncogenic pathways and strategies for targeting them.

 So, they work on the combination of the MEK inhibitors with other molecules which increase the expression of TNF-alpha and IFNandgamma;. According to the Mengyu Xie, first author of the study, these studies will help determine if modulation of the immune microenvironment along with tumor signaling is a viable treatment strategy for lung cancer patients with KRAS mutations and potentially other mutations that rely on MEK signaling.