A5053743503- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Lung Cancer Research Studies
- Cancer, Lipids, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Cell death mechanisms and regulation
- Cancer-related gene regulation
- Cancer Cells and Metastasis
- Neuroendocrine Tumor Research Advances
- Drug Transport and Resistance Mechanisms
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2020-2024
University of Cologne
2019-2024
University Hospital Cologne
2020-2024
Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate death pathways prior therapy. Yet, which these remain available SCLC is unknown. Here, through systemic analysis pathway availability SCLC, we identify non-neuroendocrine (NE) be vulnerable ferroptosis subtype-specific lipidome remodeling. While NE resistant, it acquires addiction the TRX anti-oxidant pathway. In experimental settings non-NE/NE intratumoral heterogeneity, non-NE or...
Oncogenic KRAS is the key driver oncogene for several of most aggressive human cancers. One feature oncogenic expression an early increase in cellular reactive oxygen species (ROS) which promotes transformation if cells manage to escape cell death, mechanisms remain incompletely understood. Here, we identify that as compared WT isogenic systems renders more resistant ferroptosis, a recently described type regulated necrosis. Mechanistically, find with mutant show specific lack...
Ferroptosis is a newly identified iron‐dependent type of regulated cell death that can also be regarded as caused by the specific collapse lipid antioxidant defence machinery. has gained increasing attention potential therapeutic strategy for therapy‐resistant cancer types. However, many ferroptosis‐inducing small molecules do not reach pharmacokinetic requirements their effective clinical use yet. Nevertheless, optimization under development. In this review, we summarize current...
Abstract Small cell lung cancer (SCLC) is a highly aggressive type of cancer, characterized by rapid proliferation, early metastatic spread, clinical recurrence and high rate mortality. Using in vivo insertional mutagenesis screening conjunction with cross-species genomic transcriptomic validation, we identified strong consistent signal for neuronal, synaptic, glutamatergic signaling gene sets murine human SCLC. We show that SCLC cells have the ability to develop intimate contacts neuronal...
Abstract Bi-allelic loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests strong selective pressure to inactivate regulated death pathways prior therapy. Yet, which remain available SCLC is unknown. Here, through systemic analysis pathway availability, we identify non-neuroendocrine (NE) NE subtypes segregate by their response ferroptosis, a recently described iron-dependent type necrosis. While that extrinsic apoptosis necroptosis are incapacitated, find non-NE be...
Our recent study revealed that non-neuroendocrine small cell lung cancer (SCLC) is sensitive to the induction of ferroptosis due upregulation ether lipid synthesis. While neuroendocrine SCLC resistant, it acquires addiction thioredoxin pathway. Combined redox pathway targeting therefore achieves efficient anti-tumor activity in heterogenous SCLC.
Abstract Caspase 8 regulates normal tissue homeostasis by executing apoptosis and protecting from necroptosis. Several aggressive cancers express high levels of caspase 8, yet its function in neoplastic disease remains poorly explored. Here, we find that oncogenic KRAS-driven transformation induces a transcriptional state necroptotic priming, but necroptosis itself is kept check co-upregulation 8. Mice which deleted the pancreas manifested drastic decrease precursor lesion formation...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality. PDAC expresses high levels caspase 8, central enzyme controlling various types regulated cell death. Here, using genetically engineered mouse models we find that oncogenic KRAS-driven neoplastic transformation induces transcriptional state necroptotic priming, but necroptosis itself counter selected against through co-upregulation 8. Mechanistically, expression the driver oncogene KRAS induced...