Ren Wang Peng
Biography
Prof. Ren-Wang Peng, PhD, is a Professor and Lab Head at University Hospital Bern (Inselspital) and the Faculty of Medicine, University of Bern. A translational oncologist, he specializes in lung cancer and mesothelioma, focusing on cancer stem cells and therapeutic resistance. He earned his PhD from the Chinese Academy of Sciences and completed postdoctoral work at the Max Planck Institute before joining ETH Z?rich as a Group Leader. His research bridges mechanistic insights with novel strategies to overcome drug resistance in oncogene- and non-oncogene-driven tumors.
Research Interest
His research bridges mechanistic insights with novel strategies to overcome drug resistance in oncogene- and non-oncogene-driven tumors.
Abstract
Targeting ferroptosis evasion mechanisms in KRAS-driven lung cancer: Ferroptosis is an oxidative, non-apoptotic form of cell death that is frequently inactivated in cancer, yet its regulation in oncogene-specific tumors remains poorly understood. We have identified lactate dehydrogenase B (LDHB), but not the closely related LDHA, as a noncanonical regulator of ferroptosis defense in KRAS-driven lung cancer. Using murine models and human-derived tumor cell lines, we demonstrate that LDHB silencing impairs glutathione (GSH) levels, sensitizing cancer cells to inhibitors of either GSH biosynthesis or utilization. This triggers a KRAS-pecific ferroptosis-driven synthetic lethality, characterized by increased glutamine metabolism, oxidative phosphorylation (OXPHOS), and mitochondrial reactive oxygen species (mitoROS). Furthermore, we show that LDHB suppression upregulates STAT1, a negative regulator of SLC7A11, thereby reducing SLC7A11-dependent GSH metabolism. Our findings reveal a reviously unrecognized role of LDH isoenzymes in ferroptosis resistance and provide a novel therapeutic rationale for targeting oncogene-specific ferroptosis susceptibility in KRAS-driven lung cancer.
