LKB1 inactivation occurs in a subset of esophageal adenocarcinomas and is sufficient to drive tumor cell proliferation.

Background: The incidence of esophageal adenocarcinoma (EAC) has increased over the last several decades. Apart from mutations in TP53 gene, there are little data on genetic drivers of EAC. Liver kinase B1 (LKB1) has emerged as a multifunctional tumor suppressor regulating cell growth, differentiation, and metabolism.

WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non-Small Cell Lung Cancer.

G-S checkpoint loss contributes to carcinogenesis and increases reliance upon the G-M checkpoint for adaptation to stress and DNA repair, making G-M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G-M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several preclinical tumor models, often in the molecular context of loss.

Genomic profiling toward precision medicine in non-small cell lung cancer: getting beyond EGFR.

Lung cancer remains the leading cause of cancer-related mortality worldwide. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non-small cell lung cancer (NSCLC). A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR) have been identified in NSCLC.