lgk974 and Adenocarcinoma-of-Lung

Activation of the Wnt signaling pathway promotes lung cancer progression and contributes to poor patient prognosis. The porcupine inhibitor LGK974, a novel orally bioavailable cancer therapeutic in Phase I clinical trials, induces potent Wnt signaling inhibition and leads to suppressed growth and progression of multiple types of cancers. The clinical use of LGK974, however, is limited in part due to its low solubility and high toxicity in tissues that rely on Wnt signaling for normal homeostasis. Here, we report the use of host-guest chemistry to enhance the solubility and bioavailability of LGK974 in mice through complexation with cyclodextrins (CD). We assessed the effects of these complexes to inhibit Wnt signaling in lung adenocarcinomas that are typically driven by overactive Wnt signaling. 2D

Topics: Adenocarcinoma of Lung; Animals; Antineoplastic Agents; Cell Line, Tumor; Cyclodextrins; Humans; Lung Neoplasms; Mice, Nude; Pyrazines; Pyridines; Wnt Proteins; Wnt Signaling Pathway