ArticleeLife2021
A subset of CB002 xanthine analogs bypass p53-signaling to restore a p53 transcriptome and target an S-phase cell cycle checkpoint in tumors with mutated-p53.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- Chemotherapy with a molecular rational basis, pentoxifylline as a promising antitumor drug.Annals of medicine and surgery (2012) · 2025Review
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- Shared gene targets of the ATF4 and p53 transcriptional networks.bioRxiv : the preprint server for biology · 2023Article
- Targeting Mutated p53: Naivete and Enthusiasm to Attempt the Impossible.Cancer research · 2023Article
- Shared Gene Targets of the ATF4 and p53 Transcriptional Networks.Molecular and cellular biology · 2023Article
- Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.Biomolecules · 2022Review
- Small-Molecule NSC59984 Induces Mutant p53 Degradation through a ROS-ERK2-MDM2 Axis in Cancer Cells.Molecular cancer research : MCR · 2022Article
- TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation.NAR cancer · 2022Article
- SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53.Open medicine (Warsaw, Poland) · 2022Article
- Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in TP53 occur commonly in the majority of human tumors and confer aggressive tumor phenotypes, including metastasis and therapy resistance. CB002 and structural-analogs restore p53 signaling in tumors with mutant-p53 but we find that unlike other xanthines such as caffeine, pentoxifylline, and theophylline, they do not deregulate the G2 checkpoint. Novel CB002-analogs induce pro-apoptotic Noxa protein in an ATF3/4-dependent manner, whereas caffeine, pentoxifylline, and theophylline do not. By contrast to caffeine, CB002-analogs target an S-phase checkpoint associated with increased p-RPA/RPA2, p-ATR, decreased Cyclin A, p-histone H3 expression, and downregulation of essential proteins in DNA-synthesis and DNA-repair. CB002-analog #4 enhances cell death, and decreases Ki-67 in patient-derived tumor-organoids without toxicity to normal human cells. Preliminary in vivo studies demonstrate anti-tumor efficacy in mice. Thus, a novel class of anti-cancer drugs shows the activation of p53 pathway signaling in tumors with mutated p53, and targets an S-phase checkpoint.
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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 Socratic graph.