ArticleOncogene2010
Status of p53 in human cancer cells does not predict efficacy of CHK1 kinase inhibitors combined with chemotherapeutic agents.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 53 citations in OpenAlex.
- CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma.The Journal of clinical investigation · 2012Trial
- Expression of DNA-damage response genes after exposure to high LET particles used in BNCT in glioblastoma cells with altered radiosensitivity.Scientific reports · 2025Article
- SLAYER: a computational framework for identifying synthetic lethal interactions through integrated analysis of cancer dependencies.NAR genomics and bioinformatics · 2025Article
- Chk1 Inhibition Potently Blocks STAT3 Tyrosine705 Phosphorylation, DNA-Binding Activity, and Activation of Downstream Targets in Human Multiple Myeloma Cells.Molecular cancer research : MCR · 2022Article
- Medulloblastoma and the DNA Damage Response.Frontiers in oncology · 2022Review
- Lipid raft-disrupting miltefosine preferentially induces the death of colorectal cancer stem-like cells.Clinical and translational medicine · 2021Article
- Targeting cell cycle regulation via the G2-M checkpoint for synthetic lethality in melanoma.Cell cycle (Georgetown, Tex.) · 2021Review
- Review
- The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation.Cancers · 2018Article
- ATR/CHK1 inhibitors and cancer therapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2018Review
- Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells.Neoplasia (New York, N.Y.) · 2017Article
- Targeting the ATR-CHK1 Axis in Cancer Therapy.Cancers · 2017Review
- Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53-mutated B-lymphoid cells.Oncotarget · 2016Article
- Article
- Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma.BMC cancer · 2015Article
- Molecular pathways: targeting the dependence of mutant RAS cancers on the DNA damage response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin.Cancer research · 2014Article
- Death of p53-defective cells triggered by forced mitotic entry in the presence of DNA damage is not uniquely dependent on Caspase-2 or the PIDDosome.Cell death & disease · 2013Article
- Checkpoint kinase 1 in DNA damage response and cell cycle regulation.Cellular and molecular life sciences : CMLS · 2013Review
- The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design.British journal of clinical pharmacology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage checkpoints cause cell cycle arrest, allowing DNA repair before resumption of the cell cycle. These checkpoints can be activated through several signaling pathways. Checkpoint activators include p53, checkpoint kinase 1 (CHK1), checkpoint kinase 2 and/or MAPKAP kinase 2 (MK2). Many cancer cells lack p53 activity and, therefore, depend on alternative checkpoint activators to arrest the cell cycle following DNA damage. Inhibition of these pathways is expected to specifically sensitize these p53-deficient cells to DNA damage caused by chemotherapy. Using isogenic p53-proficient and p53-deficient cancer cell lines, we show that inactivation of CHK1, but not MK2, abrogates cell cycle arrest following chemotherapy, specifically in p53-deficient cells. However, we show that CHK1 is required to maintain genome integrity and cell viability, and that p53-proficient cells are no less sensitive than p53-deficient cells to CHK1 inhibition in the presence of DNA damage. Thus, combining CHK1 inhibition with DNA damage does not lead to preferential killing of p53-deficient over p53-proficient cells, and inhibiting CHK1 does not appear to be a promising approach for potentiation of cancer chemotherapy.
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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.