Abnormalities in the KRAS gene are the most common mutations in lung cancer, especially in lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC). However, no effective targeted therapy directed at KRAS has been found. Instead, researchers have begun to focus on blocking molecules “downstream” in the chain of chemical reactions through which KRAS affects the cell. Two such molecules are TBK1 and MEK. A recent study found that the drug CYT387 blocks TBK1. CYT387 reduced tumor growth in mice with KRAS-mutant lung adenocarcinoma. Also in mice, CYT387 and the MEK inhibitor AZD6244, given together, shrank aggressive lung tumors with mutations in both the KRAS and the TP53 gene. Researchers now hope to investigate the two drugs in people.
To gain better insight into TANK-binding kinase 1 (TBK1) survival signaling, we searched for altered phosphoproteins using mass spectrometry following RNAi-mediated TBK1 knockdown. These results collectively revealed TBK1 as a mitosis regulator through activation of PLK1 and also suggested metadherin as a putative TBK1 downstream effector involved in lung cancer cell survival.