ReviewBritish journal of clinical pharmacology2013
The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design.
Review in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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
72 citing papers in PubMed, 123 citations in OpenAlex.
- A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Efficacy of Chemotherapy Following Prior PARP-Inhibitor Treatment in Patients with Ovarian Cancer.Cancer research and treatment · 2026Article
- Identification of a Proteolysis-Targeting-Chimera that Addresses Activated Checkpoint Kinase-1 Reveals its Non-Catalytic Functions in Tumor Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.iScience · 2025Review
- Clinical Progress of Targeted Therapy for Breast Cancer: A Comprehensive Review.Current cancer drug targets · 2025Review
- The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.Nature communications · 2024Article
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- The Interaction between CLSPN Gene Polymorphisms and Alcohol Consumption Contributes to Oral Cancer Progression.International journal of molecular sciences · 2024Article
- GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.Molecules (Basel, Switzerland) · 2022Review
- Article
- The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair.DNA repair · 2021Article
- A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515).Pediatric blood & cancer · 2021Article
- Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells.ACS pharmacology & translational science · 2021Article
- Activation of CDC25A phosphatase is limited by CDK2/cyclin A-mediated feedback inhibition.Cell cycle (Georgetown, Tex.) · 2021Article
- Review
- Comparative Activity and Off-Target Effects in Cells of the CHK1 Inhibitors MK-8776, SRA737, and LY2606368.ACS pharmacology & translational science · 2021Article
- GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer.Oncology reports · 2021Article
12 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
2 authors at 2 institutions in 1 country.
Funding
Abstract
Many anticancer agents damage DNA and activate cell cycle checkpoints that permit time for the cells to repair their DNA and recover. These checkpoints have undergone intense investigation as potential therapeutic targets and Chk1 inhibitors have emerged as promising novel therapeutic agents. Chk1 was initially recognized as a regulator of the G2/M checkpoint, but has since been demonstrated to have additional roles in replication fork stability, replication origin firing and homologous recombination. Inhibition of these pathways can dramatically sensitize cells to some antimetabolites. Current clinical trials with Chk1 inhibitors are primarily focusing on their combination with gemcitabine. Here, we discuss the mechanisms of, and emerging uses for Chk1 inhibitors as single agents and in combination with antimetabolites. We also discuss the pharmacodynamic issues that need to be addressed in attaining maximum efficacy in vivo. Following administration of gemcitabine to mice and humans, tumour cells accumulate in S phase for at least 24 h before recovering. In addition, stalled replication forks evolve over time to become more Chk1 dependent. We emphasize the need to assess cell cycle perturbation and Chk1 dependence of tumours in patients administered gemcitabine. These assessments will define the optimum dose and schedule for administration of these drug combinations.
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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.