ReviewJournal of hematology & oncology2022
The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.
Review in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Targeting DNA damage response to enhance cancer immunotherapy efficacy: molecular mechanisms and clinical advances.Medical oncology (Northwood, London, England) · 2025Pooled it
- The efficacy and safety of PARP inhibitors in mCRPC with HRR mutation in second-line treatment: a systematic review and bayesian network meta-analysis.BMC cancer · 2024Pooled it
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes.Chembiochem : a European journal of chemical biology · 2026Article
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Molecular Mechanisms of the Anticancer Activity of the Flavonoid Kaempferol: A Comprehensive Review.Journal of cancer prevention · 2026Review
- Fundamentals and emerging frontiers in p53-targeted drug development.Biochemistry and biophysics reports · 2026Review
- 4-Hydroxychalcone Exert the Anti-cancer Potential in Colorectal Cancer Through Targeting CDK6.Biological procedures online · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.Discover oncology · 2026Review
- Removing therapy-induced senescent cancer cells targets and potentiates the response of pancreatic cancer cells toward PARP inhibitors as maintenance therapy.Apoptosis : an international journal on programmed cell death · 2026Article
- Real-world data of PARP inhibitors in first-line maintenance for BRCA-mutated or HRD-positive advanced ovarian cancer: a multicentre retrospective study from India.Journal of ovarian research · 2026Observational
- Extracellular matrix-derived mechanical force induces CDK4/6 inhibitor resistance by inhibiting NEK10 dependent cell cycle regulation in breast cancer.International journal of surgery (London, England) · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Subtyping and risk model construction based on taurine metabolism-related genes for predicting prognosis and immune response in lung adenocarcinoma.Open medicine (Warsaw, Poland) · 2026Article
- Exploiting signal transduction pathways for cancer therapy: insights from natural products in preclinical models.Frontiers in pharmacology · 2026Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through "synthetic lethality" mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.
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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 OpenQuestion graph.