Junki Fukuda, Shinya Kosuge, Yusuke Satoh, Sho Sekiya, Ryodai Yamamura, Takako Ooshio, Taiga Hirata, Reo Sato, Kanako C Hatanaka, Tomoko Mitsuhashi, Toru Nakamura, Yoshihiro Matsuno, Yutaka Hatanaka, Satoshi Hirano, Masahiro Sonoshita
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. However, drug discovery for PDAC treatment has proven complicated, leading to stagnant therapeutic outcomes. Here, we identify Glycogen synthase kinase 3 (GSK3) as a therapeutic target through a whole-body genetic screening utilizing a '4-hit' Drosophila model mimicking the PDAC genotype. Reducing the gene dosage of GSK3 in a whole-body manner or knocking down GSK3 specifically in transformed cells suppressed 4-hit fly lethality, similar to Mitogen-activated protein kinase kinase (MEK), the therapeutic target in PDAC we have recently reported...
February 6, 2024: Cancer Science