NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer

作者：Josefina Doffo, Stefanos A. Bamopoulos, Hazal Köse, Felix Orben, Chuanbing Zang, Miriam Pons, Alexander T. den Dekker, Rutger W. W. Brouwer, Apoorva Baluapuri, Stefan Habringer, Maximillian Reichert, Anuradha Illendula, Oliver H. Krämer, Markus Schick, Elmar Wolf, Wilfred F. J. van IJcken, Iréne Esposito, Ulrich Keller, Günter Schneider, Matthias Wirth · 发表于：Proceedings of the National Academy of Sciences · 年份：2022 · DOI：10.1073/pnas.2105691119 · 被引用次数：38 · 研究领域：Ubiquitin and proteasome pathways、Immune cells in cancer、Acute Myeloid Leukemia Research

Significance Recent evidence demonstrated the existence of molecular subtypes in pancreatic ductal adenocarcinoma (PDAC), which resist all current therapies. The paucity of therapeutic options, including a complete lack of targeted therapies, underscores the urgent and unmet medical need for the identification of targets and novel treatment strategies for PDAC. Our study unravels a function of the transcription factor RUNX1 in apoptosis regulation in PDAC. We show that pharmacological RUNX1 inhibition in PDAC is feasible and leads to NOXA-dependent apoptosis. The development of targeted therapies that influence the transcriptional landscape of PDAC might have great benefits for patients who are resistant to conventional therapies. RUNX1 inhibition as a new therapeutic intervention offers an attractive strategy for future therapies.