ArticleOncogene2021
A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting MYCN Degradation by HLB-0532259 Induces Senescence in Retinoblastoma.Investigative ophthalmology & visual science · 2026Article
- Combination of CHK1 and CHK2 inhibitors exerts synergistic antitumor effects against neuroblastoma cells.Pediatric research · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer.Cancer research · 2026Article
- ARHGAP11A, a member of Rho GTPase activating protein family, as a prognostic biomarker linked to DNA damage response across pan-cancer.BMC cancer · 2025Article
- Review
- ATP6V0A4 as a novel prognostic biomarker and potential therapeutic target in oral squamous cell carcinoma.BMC oral health · 2025Article
- DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint.DNA repair · 2025Article
- ATR Inhibition Synergizes With Alkylating PI Polyamide Targeting MYCN by Suppressing DNA Repair in MYCN-Amplified Neuroblastoma.Cancer science · 2025Article
- Identifying Molecular Probes for Fluorescence-Guided Surgery in Neuroblastoma: A Systematic Review.Children (Basel, Switzerland) · 2025Review
- Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/International journal of molecular sciences · 2025Article
- A Small Molecule Selectively Targets N-Myc to Suppress Neuroblastoma Cancer Progression.International journal of biological sciences · 2025Article
- Pterostilbene inhibits non-small cell lung cancer progression by activating the STING pathway and enhancing antitumor immune response.Frontiers in immunology · 2025Article
- Article
- CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer.Cell death discovery · 2024Article
- Review
- Novel insight into histological and molecular astrocytoma, IDH-mutant, Grade 4 by the updated WHO classification of central nervous system tumors.Cancer medicine · 2023Article
- Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2023Article
- KCTD1 is a new modulator of the KCASH family of Hedgehog suppressors.Neoplasia (New York, N.Y.) · 2023Article
- Cyclers' kinases in cell division: from molecules to cancer therapy.Cell death and differentiation · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since MYCN inactivation in clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need to be explored to identify more effective and less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress and promote mitotic catastrophe, counteracted by CHK1. Here, we showed that PARP and CHK1 inhibitors synergized to induce death in neuroblastoma cells and in primary cultures of SHH-dependent medulloblastoma, their combination being more effective in MYCN amplified and MYCN overexpressing cells compared to MYCN non-amplified cells. Although the MYCN amplified IMR-32 cell line carrying the p.Val2716Ala ATM mutation showed the highest sensitivity to the drug combination, this was not related to ATM status, as indicated by CRISPR/Cas9-based correction of the mutation. Suboptimal doses of the CHK1 inhibitor MK-8776 plus the PARP inhibitor olaparib led to a MYCN-dependent accumulation of DNA damage and cell death in vitro and significantly reduced the growth of four in vivo models of MYCN-driven tumors, without major toxicities. Our data highlight the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials.
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.