ArticleCancer research2015
Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 77 papers.
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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.
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Who cites it
77 citing papers in PubMed, 107 citations in OpenAlex.
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Apoptosis signaling and cancer targeted therapy: from bench to bespoke.Translational cancer research · 2026Review
- Moxibustion Modulates ALOX15-Mediated Lipid Peroxidation to Inhibit Ferroptosis in Synovial Inflammatory Injury of Rheumatoid Arthritis.Mediators of inflammation · 2026Article
- Article
- Emerging therapeutic advancements in pancreatic cancer: a contemporary review.Discover oncology · 2025Review
- TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review).International journal of molecular medicine · 2025Review
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Covalent Modification of p53 by (ACS pharmacology & translational science · 2024Article
- Bioengineered Anthocyanin-Enriched Tomatoes: A Novel Approach to Colorectal Cancer Prevention.Foods (Basel, Switzerland) · 2024Review
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- Understanding the complexity of p53 in a new era of tumor suppression.Cancer cell · 2024Review
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Overcoming adaptive resistance in AML by synergistically targeting FOXO3A-GNG7-mTOR axis with FOXO3A inhibitor Gardenoside and rapamycin.Genes & diseases · 2024Article
- Shared gene targets of the ATF4 and p53 transcriptional networks.bioRxiv : the preprint server for biology · 2023Article
- Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles.Journal of nanobiotechnology · 2023Article
- Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS.Bioactive materials · 2023Article
- Shared Gene Targets of the ATF4 and p53 Transcriptional Networks.Molecular and cellular biology · 2023Article
- Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.Cell death & disease · 2022Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.
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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.