ArticleMolecular cancer therapeutics2024
PUMA/RIP3 Mediates Chemotherapy Response via Necroptosis and Local Immune Activation in Colorectal Cancer.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Reactivating necroptosis in colorectal cancer potentiates chemotherapy and antitumor immune responses.Cancer letters · 2026Article
- CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies.Journal of hematology & oncology · 2026Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases.Nature reviews. Molecular cell biology · 2025Review
- The Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer.Journal of respiratory biology and translational medicine · 2025Article
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Natural products target programmed cell death signaling mechanisms to treat colorectal cancer.Frontiers in pharmacology · 2025Review
- Anticancer Ribosomally Synthesized and Post-Translationally Modified Peptides from Plants: Structures, Therapeutic Potential, and Future Directions.Current issues in molecular biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Induction of programmed cell death (PCD) is a key cytotoxic effect of anticancer therapies. PCD is not confined to caspase-dependent apoptosis, but includes necroptosis, a regulated form of necrotic cell death controlled by receptor-interacting protein (RIP) kinases 1 and 3, and mixed lineage kinase domain-like (MLKL) pseudokinase. Necroptosis functions as a defense mechanism against oncogenic mutations and pathogens and can be induced by a variety of anticancer agents. However, the functional role and regulatory mechanisms of necroptosis in anticancer therapy are poorly understood. In this study, we found that RIP3-dependent but RIP1-independent necroptosis is engaged by 5-fluorouracil (5-FU) and other widely used antimetabolite drugs, and functions as a major mode of cell death in a subset of colorectal cancer cells that express RIP3. We identified a novel 5-FU-induced necroptosis pathway involving p53-mediated induction of the BH3-only Bcl-2 family protein, p53 upregulated modulator of apoptosis (PUMA), which promotes cytosolic release of mitochondrial DNA and stimulates its sensor z-DNA-binding protein 1 (ZBP1) to activate RIP3. PUMA/RIP3-dependent necroptosis mediates the in vitro and in vivo antitumor effects of 5-FU and promotes a robust antitumor immune response. Our findings provide a rationale for stimulating necroptosis to enhance tumor cell killing and antitumor immune response leading to improved colorectal cancer treatments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.