Therapeutics: Receptor-interacting serine-threonine kinase 3 (RIPK3; RIP3)

Patient sample and mouse studies suggest inhibiting RIPK3 could help treat pancreatic ductal adenocarcinoma (PDAC). In patient samples, levels of RIPK3 were higher in PDAC tumors than in the surrounding normal tissue. In mouse models of PDAC harboring oncogenic K-Ras (KRAS) and p53 mutations, Gemzar gemcitabine increased RIPK3 expression in the pancreas compared with vehicle. In a mouse model of mutant KRAS-driven PDAC, systemic RIPK3 knockout decreased disease progression and increased survival compared with normal RIPK3 expression. In mouse models of orthotopic mutant KRAS-driven PDAC or mutant KRAS- and mutant p53-driven PDAC, tumor knockout of RIPK3 decreased tumor growth. Next steps could include developing and testing RIPK3 inhibitors in models of PDAC. ...